<?xml version="1.0" encoding="UTF-8"?><rss version="2.0"
	xmlns:content="http://purl.org/rss/1.0/modules/content/"
	xmlns:wfw="http://wellformedweb.org/CommentAPI/"
	xmlns:dc="http://purl.org/dc/elements/1.1/"
	xmlns:atom="http://www.w3.org/2005/Atom"
	xmlns:sy="http://purl.org/rss/1.0/modules/syndication/"
	xmlns:slash="http://purl.org/rss/1.0/modules/slash/"
	>

<channel>
	<title>Exosome Tech &#8211; Creative Biolabs Exosome Blog</title>
	<atom:link href="https://www.creative-biolabs.com/blog/exosome/category/exosome-tech/feed/" rel="self" type="application/rss+xml" />
	<link>https://www.creative-biolabs.com/blog/exosome</link>
	<description></description>
	<lastBuildDate>Wed, 03 Apr 2024 03:34:32 +0000</lastBuildDate>
	<language>en-US</language>
	<sy:updatePeriod>
	hourly	</sy:updatePeriod>
	<sy:updateFrequency>
	1	</sy:updateFrequency>
	<generator>https://wordpress.org/?v=6.3.1</generator>

<image>
	<url>https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2020/11/cropped-favicon-32x32.png</url>
	<title>Exosome Tech &#8211; Creative Biolabs Exosome Blog</title>
	<link>https://www.creative-biolabs.com/blog/exosome</link>
	<width>32</width>
	<height>32</height>
</image> 
	<item>
		<title>Extracellular Vesicles Incorporate Retrovirus-Like Capsids for Enhanced Packaging and Systemic Delivery of mRNA to Neurons</title>
		<link>https://www.creative-biolabs.com/blog/exosome/exosome-tech/extracellular-vesicles-incorporate-retrovirus-like-capsids-for-enhanced-packaging-and-systemic-delivery-of-mrna-to-neurons/</link>
		
		<dc:creator><![CDATA[biolabs]]></dc:creator>
		<pubDate>Thu, 29 Feb 2024 09:26:50 +0000</pubDate>
				<category><![CDATA[Exosome Tech]]></category>
		<guid isPermaLink="false">https://www.creative-biolabs.com/blog/exosome/?p=278</guid>

					<description><![CDATA[The blood-brain barrier (BBB) poses a significant challenge to the systemic delivery of mRNA to diseased neurons.While extracellular vesicles (EVs) derived from leukocytes can traverse the BBB, efficiently loading lengthy mRNAs into<a class="moretag" href="https://www.creative-biolabs.com/blog/exosome/exosome-tech/extracellular-vesicles-incorporate-retrovirus-like-capsids-for-enhanced-packaging-and-systemic-delivery-of-mrna-to-neurons/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p><span style="font-size: 15px;">The blood-brain barrier (BBB) poses a significant challenge to the systemic delivery of mRNA to diseased neurons.While extracellular vesicles (EVs) derived from leukocytes can traverse the BBB, efficiently loading lengthy mRNAs into EVs and improving their uptake by neurons remains problematic. A recent collaboration between Cornell University and the Massachusetts Institute of Technology (MIT) has addressed this issue, as outlined in an article published in the journal Nature Biomedical Engineering. Their approach involves a method to enhance mRNA loading and neuronal uptake by engineering leukocytes to produce EVs containing retrovirus-like mRNA packaging shells.</span></p>
<p><span style="font-size: 15px;"><img decoding="async" fetchpriority="high" class="aligncenter wp-image-247" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/03/1.jpg" alt="" width="611" height="409" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/03/1.jpg 764w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/03/1-300x201.jpg 300w" sizes="(max-width: 611px) 100vw, 611px" /></span></p>
<p><span style="font-size: 15px;">Systemic drug delivery to neurons is limited by the BBB, as well as by low uptake rates of vectors and inefficient release onto neurons. Most biologics, including recombinant proteins, therapeutic antibodies, and nucleic acids, are unable to penetrate the BBB. Adeno-associated viruses (AAVs) can deliver DNA to neurons, while recombinant proteins and therapeutic antibodies can cross the BBB via receptor-mediated transporters specific to certain peptides, such as insulin or transferrin. Messenger RNA (mRNA) has emerged as a promising therapeutic agent for preventing and treating diseases. However, for mRNA to be effective in the body, it requires a safe, efficient, and stable delivery system that shields it from degradation and facilitates cellular uptake and release. Various viral and nonviral vectors have been developed for this purpose, including retroviral vectors, lipid nanoparticles, polymers, protein derivatives, and membrane-enclosed vesicles. However, achieving efficient and targeted delivery of RNA therapeutics <em>in vivo</em> remains a formidable challenge.</span></p>
<p><span style="font-size: 15px;">Inflammatory stimulation of the brain leads to the destruction of the BBB. Brain microvascular endothelial cells (BMECs) exhibit increased permeability, accompanied by an upregulation of leukocyte adhesion molecules. This facilitates the entry of circulating leukocyte-derived extracellular vesicles (EVs) into the brain, rendering them excellent candidates for neuron-targeted drug delivery. The permeability of the BBB to leukocyte EVs is heightened in various neurological diseases, including age-related chronic inflammation, neurodegenerative diseases, and more severe pathological conditions such as systemic inflammation and secondary injuries (e.g., stroke). However, the clinical translation of EV-based therapeutics for these diseases is limited by low payload encapsulation efficiency and the inability to control the molecules loaded into EVs from donor cells. The payload of EVs may comprise proteins, DNA, RNA, lipids, nutrients, and metabolic waste products. The exclusion of unnecessary cellular components from EVs is challenging, impacting both loading capacity and the potential delivery of harmful components to the target.</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;">Various systems have been developed for loading small RNAs (such as siRNA and miRNA) into EVs, but efficiently enriching of long mRNAs into EVs remains a challenge. Extremely low copy numbers of endogenous EV-associated RNAs have been reported, ranging from 0.02 to 1 RNA per EV. Small RNAs are more efficiently packaged into EVs compared to long mRNAs (0.01 to 1 miRNA vs. 0.001 intact long RNAs per EV). Only 8% of donor cells exhibited detectable mRNA in their EVs. Previous methods for loading mRNA into EVs include passive and active encapsulation. For example, by incubating with macrophage-derived EVs following ultrasound and extrusion, or treating with saponins to address Parkinson&#8217;s disease. However, this post-EV isolation and loading approach has limited capacity as EVs already filled with donor cell components cannot be unloaded to accommodate drugs. Alternatively, EVs can be engineered at the mother cell level. The efficient and selective incorporation of mRNA into EVs under natural conditions is crucial for designing EVs as therapeutic drug carriers.</span></p>
<p><span style="font-size: 15px;">To enhance the loading of RNA payloads into EVs, the authors introduced retrovirus-like protein shells into the EV lumen. These protein shells naturally occur in the human brain and play a role in facilitating intercellular communication within the central nervous system. They originate from transposable genomic elements spanning eukaryotic domains, known as long terminal repeat (LTR) retrotransposons, which share an evolutionary origin with retroviruses. LTR retroviruses, along with the retrotransposon coat protein (Gag) homolog Arc (activity-regulated cytoskeleton-associated protein), may have evolved in parallel and function similarly to infectious RNA retroviruses. Another Gag homolog, PEG10, was recently modified to form virus-like particles for in vitro mRNA delivery. The Arc protein self-assembles into a virus-like shell to encapsulate mRNA, which is then released from neurons and delivered to receiving neurons via receptor-mediated endocytosis. Although Arc EVs hold potential as drug delivery vectors, their use in drug delivery remains incompletely studied. Arc and Gag are reported to be inefficient at mRNA transduction and less specific for payloads without the addition of their untranslated regions (UTRs). In this study, an Arc 5’ UTR (A5U) was included in the payload build to stabilize the shell and increase payload carrying capacity. Therefore, the authors introduced the Arc protein coat into EVs and added the A5U RNA motif stabilizer to achieve effective mRNA encapsulation and delivery.</span></p>
<p><span style="font-size: 15px;">In addition to enhanced payload-carrying capabilities, the system offers several other advantages. First, engineered retrotransposon Arc extracellular vesicles (eraEVS) produced by autologous leukocytes are immunologically inert and accumulate in the inflammatory microenvironment, crossing the blood-brain barrier with the assistance of membrane molecules from donor leukocytes. Furthermore, the Arc component recruits wrapping proteins during self-assembly, promoting the cellular uptake of EVs through its natural function in mediating molecular exchange between neurons. Moreover, the virus-like shell renders eraEVs more stable than other engineered RNA-loaded EVs, protecting the payload from nuclease degradation until its release is triggered. Besides leveraging these unique virus-like properties, eraEVs are safe, serving as short-lived drug carriers incapable of replication, infection, or genetic information insertion into the recipient&#8217;s genome. Crucially, relying on the natural targeting capabilities of EVs across different cell types, eraEVs can be generated from various donor cells and applied in diverse biomedical contexts. This study highlights an endogenous virus-like system capable of loading and delivering mRNA <em>in vivo</em>, specifically targeting diseased neurons through systemic administration.</span></p>
<p style="text-align: center;"><span style="font-size: 15px;"><img decoding="async" class="aligncenter wp-image-248" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/03/2.jpg" alt="" width="629" height="690" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/03/2.jpg 1277w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/03/2-273x300.jpg 273w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/03/2-933x1024.jpg 933w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/03/2-768x843.jpg 768w" sizes="(max-width: 629px) 100vw, 629px" /><span style="font-size: 12px;">Enhanced stability of Arc EV via A5U motif</span></span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;">The study transfected immortalized and primary bone marrow-derived leukocytes with DNA or RNA encoding the activity-regulated cytoskeleton-associated protein (Arc) of coat formation and the RNA element of the Arc 5&#8242; untranslated region that stabilizes the coat. These engineered EVs inherit the endothelial adhesion molecules of donor leukocytes, recruit endogenous packaging proteins to their surface, cross the BBB, and enter sites of neuroinflammation in neurons. These EVs generated from autologous donor leukocytes are immunologically inert and enhance neuronal uptake of packaged mRNA in a mouse model of low-grade chronic neuroinflammation.</span></p>
<p>&nbsp;</p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;"><strong>Reference</strong><strong>:</strong></span></p>
<p><span style="font-size: 12px;">Gu W, Luozhong S, Cai S, et al. Extracellular vesicles incorporating retrovirus-like capsids for the enhanced packaging and systemic delivery of mRNA into neurons. Nat Biomed Eng. Published online February 19, 2024. doi:10.1038/s41551-023-01150-x</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;"><strong>Related Services:</strong></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/brain-targeted-exosome-modification-service.htm">Brain-Targeted Exosome Modification Service</a></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/central-nervous-system-cns-disorder.htm">Exosome in CNS Disorder</a></span></p>
<p>&nbsp;</p>
]]></content:encoded>
					
		
		
			</item>
		<item>
		<title>Creating Designer Engineered Extracellular Vesicles for Diverse Ligand Display, Target Recognition, and Controlled Protein Loading and Delivery</title>
		<link>https://www.creative-biolabs.com/blog/exosome/exosome-tech/creating-designer-engineered-extracellular-vesicles-for-diverse-ligand-display-target-recognition-and-controlled-protein-loading-and-delivery/</link>
		
		<dc:creator><![CDATA[biolabs]]></dc:creator>
		<pubDate>Sat, 28 Oct 2023 09:46:55 +0000</pubDate>
				<category><![CDATA[Drug Delivery]]></category>
		<category><![CDATA[Exosome Tech]]></category>
		<guid isPermaLink="false">https://www.creative-biolabs.com/blog/exosome/?p=149</guid>

					<description><![CDATA[Effective and targeted drug delivery remains a significant challenge in modern medicine. Researchers are employing biochemical engineering approaches to repurpose extracellular vesicles (EVs) as drug delivery vehicles. Studies have demonstrated that displaying<a class="moretag" href="https://www.creative-biolabs.com/blog/exosome/exosome-tech/creating-designer-engineered-extracellular-vesicles-for-diverse-ligand-display-target-recognition-and-controlled-protein-loading-and-delivery/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p><span style="font-size: 15px;">Effective and targeted drug delivery remains a significant challenge in modern medicine. Researchers are employing biochemical engineering approaches to repurpose extracellular vesicles (EVs) as drug delivery vehicles. Studies have demonstrated that displaying targeting ligands such as GalNAc on the surface of EVs and utilizing HaloTag fused to protein anchors enriched on engineered EVs can successfully target human primary hepatocytes. Moreover, studies decorating EVs with antibodies that recognizing the GLP1 cell surface receptor have shown improved targeting of EVs to cells overexpressing this receptor. The study has also enhanced the efficiency of Cre recombinase loading into the EVs chamber. These findings suggest that EVs can be engineered to improve payload loading and enable specific cell targeting, transforming them into customized drug delivery vehicles. The relevant content was published online onOctober 22 in the international advanced materials academic journal Advanced Science titled &#8220;Creating Designer Engineered Extracellular Vesicles for Diverse Ligand Display, Target Recognition, and Controlled Protein Loading and Delivery.&#8221;</span></p>
<p><span style="font-size: 15px;"><img decoding="async" class="aligncenter size-full wp-image-151" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/11/1.png" alt="" width="830" height="838" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/11/1.png 830w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/11/1-297x300.png 297w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/11/1-150x150.png 150w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/11/1-768x775.png 768w" sizes="(max-width: 830px) 100vw, 830px" /></span></p>
<p><span style="font-size: 15px;">Researchers describe the challenges of targeted delivery of drug types such as enzymes, antibodies, peptides, and nucleic acids to specific treatment sites and propose potential solutions utilizing extracellular vesicles (EVs) as drug encapsulation platforms. EVs are natural nanosized lipid bilayer particles capable of delivering bioactive molecules, inducing functional responses, and participating in intercellular communication. They are released by nearly all cell types and internalized by nearby or distant receptor cells. Compared to synthetic nanoparticles, EVs offer unique advantages, including excellent biocompatibility, stability, and low immunogenicity. They protect their cargo during circulation and their surface provides naturally occurring modification sites that enhance their functionality. However, despite these remarkable features of EVs, challenges remain, such as rapid clearance from circulation, intrinsic targeting requiring functionalization, and limited loading capacity.</span></p>
<p><span style="font-size: 15px;">Despite the breakthroughs in EV engineering, delivering EVs specifically to target cell populations remains a challenge. To overcome this, researchers modify EV surfaces to display various targeting molecules recognized by specific cells. For example, antibodies or antibody fragments have been integrated into EV surfaces, offering versatility as antibodies can be designed for any target. However, the use of monoclonal antibodies as targeting molecules is limited due to their large size and complexity.</span></p>
<p><span style="font-size: 15px;">Most cell engineering strategies focus on directing targeting peptides and proteins to EV protein sorting domains, such as Lamp2b, tetraspanin, and PTGFRN. However, incorporating more complex molecules using this approach is challenging. An alternative method involves modifying the EV surfaces through cross-linking reactions, such as azide-alkyne cycloaddition or click chemistry, to attach targeting molecules covalently. This technique is suitable for introducing large molecules, small molecules, sugars, or polysaccharides onto EV surfaces. Some targeting peptides, such as epidermal growth factor or those with high affinity for integrin αvβ3, have been successfully introduced using this method.</span></p>
<p><span style="font-size: 15px;">Another obstacle in utilizing EVs as drug delivery vehicles is delivering drug payloads and proteins into recipient cells&#8217; cytoplasm. Studies have demonstrated that light- and small-molecule-induced dimerization systems can increase cargo protein load, such as SpCas9 and Cre recombinase, within EVs. However, releasing proteins inside EVs during genetic engineering remains challenging and requires additional stimulation.</span></p>
<p><span style="font-size: 15px;">In this study, researchers employed a variety of state-of-the-art genetic engineering methods to modify EV compositions, enhancing cell targeting and loading. Specifically, EV surfaces were decorated by attaching a vesicle-anchored protein fused to a modified haloalkane dehalogenase protein tag (HaloTag). This tag covalently binds to synthetic ligands carrying chlorinated alkane linkers, allowing the introduction of various molecular effectors such as fluorescent dyes, peptides, sugars, and small molecules on to EV surfaces. The researchers used this system to decorate purified EVs with trivalent N-acetylgalactosamine (GalNAc) and demonstrated that these engineered EVs preferentially bind to primary human hepatocytes. The research also developed a complementary system to display antibodies on EV surfaces.</span></p>
<p><span style="font-size: 15px;">Additionally, two protein engineering approaches were employed to enhance Cre recombinase loading and protein release into EV lumens during genetic engineering. These modified EVs deliver functional Cre into recipient cell cytoplasm after treatment with endosomal escape enhancers. Importantly, these modifications do not alter EVs&#8217; fundamental properties. When injected into mice, the engineered EVs were well tolerated, exhibiting no detectable liver toxicity. Overall, these findings underscore the significant potential of engineered EVs as unique protein-targeting therapeutic drug delivery systems.</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;"><strong>Reference:</strong></span></p>
<p><span style="font-size: 15px;">Ivanova A, Badertscher L, O&#8217;Driscoll G, et al. Creating Designer Engineered Extracellular Vesicles for Diverse Ligand Display, Target Recognition, and Controlled Protein Loading and Delivery [published online ahead of print, 2023 Oct 22]. Adv Sci (Weinh). 2023;e2304389. doi:10.1002/advs.202304389</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;"><strong>Related Services:</strong></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/exosome-display.htm">Exosome Display</a></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/cargo-loading-into-exosomes.htm">Exosome Cargo Loading Services</a></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/exosome-display-based-targeted-delivery.htm">Exosome Display-based Targeted Delivery</a></span></p>
]]></content:encoded>
					
		
		
			</item>
		<item>
		<title>Identifying of Scaffold Proteins to Enhance Endogenous Engineering of Extracellular Vesicles</title>
		<link>https://www.creative-biolabs.com/blog/exosome/exosome-tech/identifying-of-scaffold-proteins-to-enhance-endogenous-engineering-of-extracellular-vesicles/</link>
		
		<dc:creator><![CDATA[biolabs]]></dc:creator>
		<pubDate>Mon, 28 Aug 2023 09:11:50 +0000</pubDate>
				<category><![CDATA[Exosome Tech]]></category>
		<guid isPermaLink="false">http://www.creative-biolabs.com/blog/exosome/?p=110</guid>

					<description><![CDATA[Extracellular vesicles (EVs) have emerged as a promising avenue for advanced drug delivery. One effective strategy for loading these EVs with desired cargo involves genetically fusing a target protein to a scaffold<a class="moretag" href="https://www.creative-biolabs.com/blog/exosome/exosome-tech/identifying-of-scaffold-proteins-to-enhance-endogenous-engineering-of-extracellular-vesicles/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p><span style="font-size: 15px;">Extracellular vesicles (EVs) have emerged as a promising avenue for advanced drug delivery. One effective strategy for loading these EVs with desired cargo involves genetically fusing a target protein to a scaffold protein with exceptional EV sorting capabilities. To address the challenge of finding suitable scaffolding proteins, a recent article published in the journal <em>Nature Communications</em> has focused on identifying superior candidates. This research aims to enhance capacity of extracellular vesicles to transport specific cargo.</span></p>
<p><span style="font-size: 15px;"><img decoding="async" loading="lazy" class="aligncenter  wp-image-111" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/1.jpg" alt="" width="599" height="242" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/1.jpg 858w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/1-300x121.jpg 300w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/1-768x310.jpg 768w" sizes="(max-width: 599px) 100vw, 599px" /></span></p>
<p><span style="font-size: 15px;">Extracellular vesicles are membrane-coated particles that various cell types release. These tiny vesicles play a crucial role in intercellular communication by transporting an array of macromolecules. Their innate tropism and protective characteristics shield their internal contents from rapid degradation. Combined with their favorable safety profile, extracellular vesicles have garnered significant attention as a potential next-generation therapeutic approach for a wide range of diseases.</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;">The therapeutic potential of exosomes primarily hinges on their cargo. In the simplest scenario, extracellular vesicles naturally carry therapeutic molecules derived from their parent cells. For instance, mesenchymal stem cell-derived EVs have consistently exhibited the regenerative and immunomodulatory properties associated with their source cells. Alternatively, extracellular vesicles can be intentionally loaded with specific molecules through either endogenous or exogenous methods. Exogenous loading involves the manipulation of pre-isolated EVs through physical techniques like ultrasound, electroporation, or chemical covalent bonding. However, this method is generally limited to smaller payloads, including miRNAs and low molecular weight chemicals, and presents challenges related to RNA precipitation and potential physical damage or aggregation of EVs. Conversely, larger payloads, such as proteins, are typically loaded endogenously within the producer cells. In this approach, the cells are genetically modified to express the target protein fused with EV sorting proteins. This modification enhances the sorting of endogenous cargo proteins and can direct molecules to the surface or lumen of EVs. Notably, intraluminal loading prevents premature dissociation/degradation of cargo, making it the preferred method for molecules susceptible to degradation or those functioning within the recipient cell&#8217;s cytoplasm or nucleus. Studies have verified the feasibility of endogenous loading by incorporating or coating protein therapeutics (such as super-inhibitory IκB and receptor protein decoys) on EVs. Furthermore, this approach allows indirect loading of RNA therapeutics through the fusion of RNA-binding proteins to EV sorting proteins.</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;">Although endogenous loading is a versatile strategy, it is essentially determined by the abundance of sorted proteins within the EV population. This determination not only hinges on the level of these proteins within each EV but also, more crucially, on their distribution across different EV subpopulations. In general, EV populations are complex and heterogeneous groups, which, until recently, have presented challenges in terms of characterization and physical separation into distinct subpopulations. This complexity has made the implementation of endogenous loading strategies more intricate. Fortunately, a breakthrough has been made with the discovery of 213 conserved proteins in EVs derived from 60 different cell types, as identified by the National Cancer Institute (NCI-60). These proteins now stand as potential candidates for EV sequencing. However, it&#8217;s worth noting that, to date, only a handful of proteins have been well characterized for their capacity to load into EVs. Most of these proteins belong to the tetraspanning superfamily and are characterized as multichannel transmembrane proteins, including well-known examples such as CD9, CD63, and CD81. Considering the inherent diversity of EVs, experiments involving the overexpression of the 63-GFP fusion protein have demonstrated that, in most cases, this resulted in 51% of particles being GFP-positive. Ongoing efforts have been made to identify alternative EV sorting candidates that show promise. These candidates include PTGFRN, BASP1, and TSPAN14. It&#8217;s important to note that these studies have primarily employed low-throughput, GFP-centered quantitative methods and have considered up to 14 candidate proteins in their investigations.</span></p>
<p style="text-align: center;"><span style="font-size: 15px;"><img decoding="async" loading="lazy" class=" wp-image-112 alignnone aligncenter" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/2.jpg" alt="" width="640" height="387" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/2.jpg 800w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/2-300x182.jpg 300w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/2-768x465.jpg 768w" sizes="(max-width: 640px) 100vw, 640px" /></span><span style="font-size: 12px;">Bioluminescent screening protocol for quantifying luminal cargo proteins in EVs</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;">In this study, a large-scale comparative analysis was conducted involving 244 potential candidates to get a more comprehensive understanding and to potentially identify other EV sorting proteins. Throughout the research, TSPAN2, TSPAN3, and CD63 consistently emerged as efficient EV sorting proteins with robust intraluminal loading capabilities across various producer cell types. Furthermore, TSPAN2 and TSPAN3 engineered EVs exhibited not only effective uptake capabilities in vitro and in vivo but also demonstrated versatile delivery possibilities, including surface display and intraluminal cargo loading. Consequently, the authors believe that this discovery forms the basis for endogenous engineering approaches aimed at loading cargo into EVs for potential therapeutic applications.</span></p>
<p style="text-align: center;"><span style="font-size: 15px;"><img decoding="async" loading="lazy" class="aligncenter  wp-image-113" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/3.jpg" alt="" width="619" height="627" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/3.jpg 771w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/3-296x300.jpg 296w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/3-768x778.jpg 768w" sizes="(max-width: 619px) 100vw, 619px" /></span><span style="font-size: 12px;">Biological activity of TSPAN2 and TSPAN3 engineered EVs</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;">This study employed a straightforward and dependable assay capable of distinguishing between intravesicular and surface cargo proteins as well as non-vesicular proteins. The study screened 244 candidate proteins to identify 24 with consistent EV sorting capabilities across five producer cell types. TSPAN2 and TSPAN3 emerged as top candidates, surpassing the performance of the CD63 scaffold. Importantly, these engineered EVs showed potential as delivery vehicles in both cell culture and mice models, facilitating the efficient transfer of luminal cargo proteins and the surface display of different functional entities. The discovery of these scaffolds establishes a foundation for EV-based engineering.</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;"><strong>References:</strong></span></p>
<p><span style="font-size: 12px;">Zheng W, Rädler J, Sork H, Niu Z, Roudi S, Bost JP, Görgens A, Zhao Y, Mamand DR, Liang X, Wiklander OPB, Lehto T, Gupta D, Nordin JZ, El Andaloussi S. Identification of scaffold proteins for improved endogenous engineering of extracellular vesicles. Nat Commun. 2023 Aug 7;14(1):4734. doi: 10.1038/s41467-023-40453-0. PMID: 37550290; PMCID: PMC10406850.</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;"><strong>Related Services:</strong></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/exosome-labeling.htm">Exosome Labeling Services</a></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/cargo-loading-into-exosomes.htm">Exosome Cargo Loading Services</a></span></p>
]]></content:encoded>
					
		
		
			</item>
		<item>
		<title>The Value of Glycosylation Modifications on Extracellular Vesicles in Vesicle Isolation Analysis and Clinical Detection</title>
		<link>https://www.creative-biolabs.com/blog/exosome/exosome-tech/the-value-of-glycosylation-modifications-on-extracellular-vesicles-in-vesicle-isolation-analysis-and-clinical-detection/</link>
		
		<dc:creator><![CDATA[biolabs]]></dc:creator>
		<pubDate>Wed, 28 Jun 2023 09:42:26 +0000</pubDate>
				<category><![CDATA[Exosome Tech]]></category>
		<guid isPermaLink="false">http://www.creative-biolabs.com/blog/exosome/?p=115</guid>

					<description><![CDATA[Recent studies have revealed that extracellular vesicles (EVs) surface molecules are often accompanied by glycan or glycosylation modifications. Researchers from the Institute of Chemistry at the Slovak National Academy of Sciences have<a class="moretag" href="https://www.creative-biolabs.com/blog/exosome/exosome-tech/the-value-of-glycosylation-modifications-on-extracellular-vesicles-in-vesicle-isolation-analysis-and-clinical-detection/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p><span style="font-size: 15px;">Recent studies have revealed that extracellular vesicles (EVs) surface molecules are often accompanied by glycan or glycosylation modifications. Researchers from the Institute of Chemistry at the Slovak National Academy of Sciences have published a research-based review that discusses the role of glycosylation in EV formation, loading, and release. They describe methods for glycan identification and glycan-based analysis to capture EVs and achieve high-sensitivity detection. In addition, the researchers provide detailed insights into EV glycans and glycan-processing enzymes as potential biomarkers, therapeutic targets, or tools for regenerative medicine applications. This relevant content was published online on June 10th in Biotechnology Advances, an international academic journal in the field of bioengineering, titled &#8220;Glycosylation in Extracellular Vesicles: Isolation, Characterization, Composition, Analysis and Clinical Applications.&#8221;</span></p>
<p><img decoding="async" loading="lazy" class="aligncenter  wp-image-116" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/1-1.jpg" alt="" width="674" height="336" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/1-1.jpg 1778w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/1-1-300x149.jpg 300w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/1-1-768x383.jpg 768w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/1-1-1024x510.jpg 1024w" sizes="(max-width: 674px) 100vw, 674px" /></p>
<p><span style="font-size: 15px;"><strong>An outline of this review includes:</strong></span></p>
<ul>
<li><span style="font-size: 15px;">Glycans&#8217; crucial role in EV formation, loading and release.</span></li>
<li><span style="font-size: 15px;">Formation of a biomolecular corona with a thickness of 5-70 nm by the glycan component of EVs.</span></li>
<li><span style="font-size: 15px;">Detection of 1 extracellular vesicle per microliter under anhydrous conditions using the mannan method.</span></li>
<li><span style="font-size: 15px;">Primarily analyzing glycans in extracellular vesicles are primarily analyzed using lectin microarrays that incorporate up to 45 lectins.</span></li>
<li><span style="font-size: 15px;">Promising applications of glycans in extracellular vesicles have promising applications as biomarkers.</span></li>
</ul>
<p>&nbsp;</p>
<p><span style="font-size: 15px;">Extracellular vesicles (EVs) are lipid bilayer-bound vesicles secreted into the extracellular space by different cells. EVs play pivotal roles in intercellular communication, gene expression regulation, reproduction, cell development and proliferation, wound healing, waste management, metabolic regulation and reprogramming, signal transduction, immune response, apoptosis, and cancer initiation and progression. Two primary subpopulations of EVs exist: including exocytic particles (ectosomes, 50-10,000 nm) formed by membrane budding on the plasma membrane, and exosomes (30-150 nm) budding inwardly through endosomal membranes in cells. Moreover, other types of EVs have also been described, including migratory bodies (500–3,000 nm), secretory autophagosomes and autophagic endosomes, exosomes (1,000–10,000 nm) and apoptotic bodies (50-5,000 nm), among others.</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;">Traditional EV isolation methods encompass ultracentrifugation, particle size separation chromatography, precipitation, extraction, ultrafiltration, immunoaffinity capture, microfluidics, and charge-based separation techniques. An increasingly utilized method is bio-affinity capture of EVs using antibodies against EV surface receptors, such as CD9 immobilized on magnetic beads (MB). Direct comparisons have shown that covalently immobilized antibodies on MBs outperform streptavidin-conjugated MBs coated with biotin-modified antibodies. The researchers suggest adopting a &#8220;cocktail&#8221; isolation strategy that combines multiple isolation methods for high purity and isolation yield. This review also delves into MB-based EV isolation strategies and affinity-based methods, and other nanoparticles (NPs) used for EV isolation, including glycan-based methods.</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;">Maintaining the structural integrity of isolated EVs is crucial. Traditional buffers such as phosphate-buffered saline (PBS) are discouraged for EV storage, even for diluted EVs, as EV dispersion in PBS is unstable. Instead, the authors recommend dispersing EVs in PBS supplemented with trehalose and human serum albumin, followed by EV processing and long-term storage at -80°C. As EVs are a diverse particle type, a range of instrumental techniques is required for their study, including photonics and biophotonics (Raman spectroscopy, Fourier transform infrared spectroscopy, surface plasmon resonance, flow cytometry, fluorescence imaging), and other techniques (electron microscopy, atomic force microscopy, nanoparticle tracking analysis, nuclear magnetic resonance, dynamic light scattering, mass spectrometry, microfluidics, etc.). These techniques not only facilitate the study of EV composition, size, and number but also enable the identification of specific markers. While fluorescent dyes can visualize EVs, labeling EVs requires optimization, as some commonly used fluorochromes only label a small fraction of EVs, and these dyes tend to aggregate, not associating effectively with EVs.</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;">Moreover, membrane-bound surface proteins, known as glycoproteins, can be effectively employed for EV isolation and detection. For example, prostate-specific membrane antigen, a well-known prostate cancer biomarker, is notably enriched in prostate-derived exosomes found in urine. Similarly, other cancer biomarkers like human epidermal growth factor receptor 2 (HER2 or CD340 or erbB-2) can serve therapeutic purposes, although not all cells express this receptor. Beyond proteins and lipids, the surface of EVs showcases a diverse array of glycoconjugates, encompassing O-glycans, N-glycans, glycolipid gangliosides, and other glycan types, all suitable for EV isolation. Leveraging the principle of glycans on EV surface, lectin-based affinity chromatography has been employed successfully to isolate of intact EVs (124-134 nm) produced by cell lines from sponge-like polymers. Notably, studies have demonstrated that even Evs originating from the same cell type and size exhibit heterogeneity in the glycans expressed on their surfaces, enabling the classification of EVs based on their surface glycan features.</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;">Within this review, the researchers comprehensively outline the pivotal role of glycans in the formation, loading, and release of EVs, typically ranging in size from 100-200 nm. Glycans, as components of EV membranes, generate biomolecular coronas with a thickness ranging from 5 to 70 nm, offering an effective avenue for EV separation, particularly through magnetic particles. The review presents compelling evidence supporting the utilization of EV glycans in liquid biopsies, therapeutic applications, and regenerative medicine. The emergence of glycans in diverse fields is anticipated, particularly as our understanding of the biomolecular corona present on EVs expands. Research into the clinical applications of EV glycans is experiencing exponential growth. The robustness of EV glycan-based diagnosis necessitates validation in hundreds of samples, ensuring reliability when the AUC value exceeds 0.8. While various nanoparticles, especially magnetic nanoparticle types, have been employed for EV isolation and characterization, it is foreseeable that nanoparticles play a pivotal role in highly sensitive and robust glycan analysis, facilitating the direct visualization of on-membrane and EV-bound glycans within a molecular corona.</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;">Looking ahead, EV glycans are poised to demonstrate their potential as clinical biomarkers for numerous diseases, including various forms of cancer. Thus far, the direct in situ visualization of glycans containing sialic acid residues on EVs has only been achievable through metabolic glycan labeling. A significant future advancement will encompass tools enabling the <em>in situ</em> visualization of other carbohydrates types(such as caramel) commonly associated with various diseases. A current major development involves the ability to determine whether a protein of interest, such as PD-L1, contains glycans containing sialic acid residues. Two approaches have surfaced for tailoring the glycosylation of EVs to meet specific requirements. The first approach involves the modification of EVs using hyaluronic acid, combined with metabolic glycan labeling, enabling the modified EVs to target cells within selected tissues. The second approach entails the introduction of glycosylation domains into receptors present on EVs, followed by glycosylation of these domains using glycan processing enzymes (glycosyltransferases or glycosidases).</span></p>
<p style="text-align: center;"><img decoding="async" loading="lazy" class="aligncenter  wp-image-117" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/2-1.jpg" alt="" width="630" height="244" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/2-1.jpg 3140w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/2-1-300x116.jpg 300w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/2-1-768x297.jpg 768w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/09/2-1-1024x396.jpg 1024w" sizes="(max-width: 630px) 100vw, 630px" /><span style="font-size: 12px;">Multiple approaches used to identify glycan modifications of PD-L1 on the EV surface</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;"><strong>References:</strong></span></p>
<p><span style="font-size: 12px;">Vrablova V, Kosutova N, Blsakova A, Bertokova A, Kasak P, Bertok T, Tkac J. Glycosylation in extracellular vesicles: Isolation, characterization, composition, analysis and clinical applications. Biotechnol Adv. 2023 Oct; 67:108196. doi: 10.1016/j.biotechadv.2023.108196. Epub 2023 Jun 10. PMID: 37307942.</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;"><strong>Related Services:</strong></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/glycosylated-exosome-detection-services.htm">Glycosylated Exosome Detection Services</a></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/high-throughput-exosomal-lectin-chip-detection-service.htm">High-Throughput Exosomal Lectin Chip Detection Service</a></span></p>
]]></content:encoded>
					
		
		
			</item>
		<item>
		<title>Single-Molecule Localization Microscopy for Investigating Small Extracellular Vesicles</title>
		<link>https://www.creative-biolabs.com/blog/exosome/exosome-tech/single-molecule-localization-microscopy-for-investigating-small-extracellular-vesicles/</link>
		
		<dc:creator><![CDATA[biolabs]]></dc:creator>
		<pubDate>Sat, 28 Jan 2023 09:03:34 +0000</pubDate>
				<category><![CDATA[Exosome Tech]]></category>
		<guid isPermaLink="false">https://www.creative-biolabs.com/blog/exosome/?p=156</guid>

					<description><![CDATA[Small extracellular vesicles (sEVs) play a pivotal role as universal mediators of intercellular communication, emanating from diverse cell types. Despite extensive studies shedding light on the involvement of sEVs in various health<a class="moretag" href="https://www.creative-biolabs.com/blog/exosome/exosome-tech/single-molecule-localization-microscopy-for-investigating-small-extracellular-vesicles/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p><span style="font-size: 15px;">Small extracellular vesicles (sEVs) play a pivotal role as universal mediators of intercellular communication, emanating from diverse cell types. Despite extensive studies shedding light on the involvement of sEVs in various health and disease contexts, the intricacies of sEV biogenesis and uptake mechanisms have remained elusive due to the limitations of conventional imaging techniques. While traditional fluorescence microscopy has historically been employed for functional studies of sEVs, its restricted resolution has hindered a comprehensive understanding of these processes. Recent advancements in super-resolution microscopy, notably single-molecule localization microscopy (SMLM), offer a promising avenue for unraveling subcellular intricacies at the nanometer scale. Researchers from the University Hospital Essen in Germany delved into the fundamental principles of SMLM, emphasizing the use of suitable fluorophores with exceptional blinking properties. Their work, published in <em>Small</em> on January 12 under the title &#8220;Single Molecule Localization Microscopy for Studying Small Extracellular Vesicles,&#8221; comprehensively reviews the current application status of SMLM in the realm of sEV biology.</span></p>
<p style="text-align: center;"><span style="font-size: 15px;"><img decoding="async" loading="lazy" class="size-full wp-image-158 alignnone" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/12/2.jpg" alt="" width="1367" height="904" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/12/2.jpg 1367w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/12/2-300x198.jpg 300w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/12/2-1024x677.jpg 1024w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/12/2-768x508.jpg 768w" sizes="(max-width: 1367px) 100vw, 1367px" /></span><span style="font-size: 12px;"><strong>Figure: Principle of single-molecule localization microscopy </strong>a) Switchable fluorescent nanogroup-labeled sEVs; b) Fluorescent molecules (green dot) imaged with optical microscopy appear as a blurred point, often called a point spread function (PSF), that extends to multiple pixels in the acquired image; c) SMLM utilizes fluorophores to randomly switch between an active state and one or more inactive states; d) In SMLM, the peak of maximum intensity is detected and marked as the centroid of the image to determine the exact location of the emitting fluorophore.</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;">Extracellular vesicles (EVs) are lipid bimolecule-bound vesicles secreted into the extracellular space by all types of cells. EVs are roughly divided into three main types, including exosomes (30-150 nm), microvesicles (150-1000 nm) and apoptotic bodies (1-5µm). Acknowledging the heterogeneity of EVs, the MISEV2018 guidelines advocate the use of the term small EVs (sEVs) for vesicles smaller than 200 nm in diameter. Laden with essential cargo biomolecules such as nucleic acids, proteins, and lipids, sEVs emerge as functional mediators of intercellular communication in both health and disease. Notably, sEVs derived from tumor cells harbor disease-specific constituents, reflecting the pathological status and progression. In the tumor microenvironment, sEVs facilitate the transfer of their cargo from tumors to stromal cells, playing pivotal roles in various diseases, including neurodegenerative disorders and infections, while delivering modulators of many biological processes and affecting the immune system.</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;">Over the past decade, research on sEV biogenesis pathways and the role of sEVs in health and disease has grown exponentially. However, studies exploring the interactions of released sEVs and their cargo with cellular biomolecules in distal recipient cells have been severely hampered by the limitations of conventional microscopy techniques. Current studies predominantly utilize traditional confocal microscopy, generating 2D or 3D reconstructed images with Imaris. However, these images, although informative about sEV communication, lack the precision required to discern the exact localization and interaction of sEV-related cargo with cellular biomolecules in the 200-300 nm range. Recent revelations, such as the interaction between EV-DNA from acute myeloid leukemia (AML) and bone marrow-derived mesenchymal stromal cells (BM-MSCs), highlight the need for enhanced imaging techniques. Despite utilizing 2D confocal imaging, the identification of the specific cellular biomolecules in bone marrow mesenchymal stem cells interacting with AML EV-DNA remains elusive. Therefore, the imperative to employ super-resolution microscopy (SRM) becomes evident, particularly single-molecule localization microscopy (SMLM), with innovative labeling strategies enabling optical resolution at the nanometer range.</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;">In the realm of SRM techniques, SMLM stands out for its exceptional resolution and high signal-to-noise ratio, making it particularly advantageous for spatially quantifying the arrangement of single molecules in EV research. However, the current application of SMLM in EV research primarily involves labeling common sEV markers using antibodies linked to different fluorophores. Consequently, the functional exploration of sEVs in distal recipient cells remains very limited. Researchers have endeavored to deploy SMLM to investigate the interaction of sEV-associated DNA cargo with cellular components in distal recipient cells, yet face challenges attributed to the limitations of commonly used fluorophores.</span></p>
<p><span style="font-size: 15px;">​</span></p>
<p><span style="font-size: 15px;">This comprehensive review builds upon prior studies, addressing the pitfalls and limitations of existing labeled fluorophores. It advocates for the adoption of alternative fluorophores with specific scintillation properties in SMLM sEV imaging. The discussion encompasses the translation of SMLM technology for cell imaging into the domain of sEV imaging through diverse labeling strategies, facilitating the study of sEV biogenesis and their biomolecular interactions with distant recipient cells. The review also outlines future advances in live and fixed cell imaging of sEVs at the nanoscale resolution, addressing key questions in sEV biology, including the packaging of diverse biomolecule cargos into sEVs, the uptake of single sEVs, and the molecular interactions of sEVs with specific cellular compartments.</span></p>
<p style="text-align: center;"><span style="font-size: 15px;"><img decoding="async" loading="lazy" class="aligncenter  wp-image-157" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/12/1.jpg" alt="" width="816" height="539" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/12/1.jpg 1367w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/12/1-300x198.jpg 300w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/12/1-1024x676.jpg 1024w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2023/12/1-768x507.jpg 768w" sizes="(max-width: 816px) 100vw, 816px" /><span style="font-size: 12px;"><strong>Schematic diagram of super-resolution microscopy technology </strong>a) Timeline of major breakthroughs in optical microscopy; b) The SMLM method is based on continuously imaging the sparse signals of fluorophores and calculating their positions from the obtained diffraction patterns.</span></span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;"><strong>Reference:</strong></span></p>
<p><span style="font-size: 15px;">Ghanam J, Chetty VK, Zhu X, et al. Single Molecule Localization Microscopy for Studying Small Extracellular Vesicles. Small. 2023;19(12):e2205030. doi:10.1002/smll.202205030</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;"><strong>Related Services:</strong></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/single-cell-exosome-combined-research-services.htm">Single-Cell &amp; Exosome Combined Research Services</a></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/exosome-fluorescent-labeling.htm">Exosome Fluorescent Labeling Service</a></span></p>
]]></content:encoded>
					
		
		
			</item>
		<item>
		<title>Lung Mesenchymal Cells Secrete Lipids through Exosome-Like Vesicles to Promote Breast Cancer Lung Metastasis</title>
		<link>https://www.creative-biolabs.com/blog/exosome/exosome-tech/lung-mesenchymal-cells-secrete-lipids-through-exosome-like-vesicles-to-promote-breast-cancer-lung-metastasis/</link>
		
		<dc:creator><![CDATA[biolabs]]></dc:creator>
		<pubDate>Wed, 28 Dec 2022 09:33:56 +0000</pubDate>
				<category><![CDATA[Exosome Tech]]></category>
		<guid isPermaLink="false">https://www.creative-biolabs.com/blog/exosome/?p=196</guid>

					<description><![CDATA[It is well known that tumor metastasis relies on microenvironmental support from remote organs. However, the mechanisms through which metabolism regulates the tumor metastasis microenvironment remain undetermined. Recently, researchers discovered that lung<a class="moretag" href="https://www.creative-biolabs.com/blog/exosome/exosome-tech/lung-mesenchymal-cells-secrete-lipids-through-exosome-like-vesicles-to-promote-breast-cancer-lung-metastasis/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p><span style="font-size: 15px;">It is well known that tumor metastasis relies on microenvironmental support from remote organs. However, the mechanisms through which metabolism regulates the tumor metastasis microenvironment remain undetermined. Recently, researchers discovered that lung mesenchymal cells, rich in lipids, deliver lipids to tumor cells and NK cells via exosome-like vesicles. This process reshapes the pre-tumor microenvironment, promoting breast cancer lung metastasis. The relevant research published in the journal <em>Cell Metabolism</em> titled &#8220;Lipid-laden lung mesenchymal cells foster breast cancer metastasis via metabolic reprogramming of tumor cells and natural killer cells.&#8221;</span></p>
<p><img decoding="async" loading="lazy" class="aligncenter  wp-image-197" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/01/1-1.jpg" alt="" width="667" height="667" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/01/1-1.jpg 996w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/01/1-1-300x300.jpg 300w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/01/1-1-150x150.jpg 150w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/01/1-1-768x768.jpg 768w" sizes="(max-width: 667px) 100vw, 667px" /></p>
<p><span style="font-size: 15px;">Ninety percent of solid tumor-related deaths result from metastasis to distant vital organs and recurrence after treatment. Among the multiple steps of tumor metastasis, the colonization of disseminated tumor cells (DTCs) in distant organs is an inefficient and speed-limited step. Only a small proportion of DTCs can evade powerful immune surveillance, spread from the primary tumor site, survive in new environments, and ultimately colonize distant organs. A series of major advances in tumor metastasis research have revealed complex interactions between DTCs and organ premetastatic niches, crucial for metastatic lesion development. However, the metabolic regulation of DTCs by the organ microenvironment remains unclear.</span></p>
<p><span style="font-size: 15px;">Limited evidence supports the concept of metabolic regulation in organ niche colonization in preclinical tumor models. In breast cancer lung metastasis models, pyruvate in lung interstitial fluid is absorbed by DTCs, initiating a metabolic cascade that reshapes the extracellular matrix and facilitates lung metastasis niche information. In ovarian cancer models, omental adipocytes provide energy to DTCs through fatty acid oxidation (FAO) or activate survival and proliferation-related signaling pathways, promoting ovarian cancer metastasis to the omentum. These results highlight the organ microenvironment&#8217;s novel role in metabolically supporting DTC colonization.</span></p>
<p><span style="font-size: 15px;">The lung, among the organs prone to solid tumor occurrence, is a common metastatic site. Previous studies in the lung microenvironment have shown that neutral lipids in infiltrating innate immune cells promote tumor metastasis, contributing pre- and post-metastatic niche formation.</span></p>
<p><span style="font-size: 15px;">This study focused on lung mesenchymal cells (MCs), revealing high levels of intracellular triglyceride (TG) content in both disease-free and tumor-bearing states. The researchers studied TG in one type of lung MCs, adipose fibroblasts, finding that TG protects alveoli from oxidative damage and provides a substrate for lung surfactant synthesis during alveolar development. However, the role of lung MC-derived neutral lipids in pathological processes remains unknown. Therefore, the researchers used a breast cancer mouse model to study the mechanism by which lung MCs regulate breast cancer lung metastasis through neutral lipid metabolism.</span></p>
<p><span style="font-size: 15px;">In this breast cancer model, researchers found that lung MCs accumulated large amounts of neutral lipids during the pre-metastatic stage, mediated by interleukin-1β (IL-1β)-mediated hypoxia-induced lipid droplet-associated protein (HILPDA). This subsequently inhibited adipose triglyceride lipase (ATGL) activity in lung MCs. Knockout of MC-specific ATGL or HILPDA genes in mice enhanced and reduced breast cancer lung metastasis, respectively, suggesting a metastasis-promoting role of lipid-containing MCs. Mechanistically, lipid-containing MCs transport lipids to tumor cells and natural killer cells (NK) through exosome-like vesicles, leading to tumor cell survival and proliferation and enhancing NK cell dysfunction. Blocking IL-1β alone significantly tumor suppressed tumors and enhanced the immunotherapeutic efficacy of NK cells, mitigating lung metastasis. Overall, lung MCs regulate tumor cell progression and anti-tumor immunity through lipid metabolism, promoting breast cancer lung metastasis.</span></p>
<p><span style="font-size: 15px;">Although researchers found that neutral lipids, after being transported out of lipid-rich MCs, undergo different fates in tumor cells and NK cells, the underlying molecular mechanisms remain unknown. Additionally, <em>in situ</em> identification of lipid sources, stimulating factors for lipid release from MCs, and lipid transport between cells in different lung environments require further exploration. Despite exosome-like vesicles mediating functional reprogramming of tumor cells and NK cells, the exact metabolites derived from extracellular vesicles remain unidentified. Lipid-containing MCs have only been studied in lung metastasis models, and researchers will continue to explore their role in other contexts such as homeostasis, inflammation, lung cancer, and other lung diseases.</span></p>
<p style="text-align: center;"><img decoding="async" loading="lazy" class="aligncenter  wp-image-198" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/01/2-2.jpg" alt="" width="749" height="398" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/01/2-2.jpg 1360w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/01/2-2-300x159.jpg 300w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/01/2-2-1024x544.jpg 1024w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/01/2-2-768x408.jpg 768w" sizes="(max-width: 749px) 100vw, 749px" /><span style="font-size: 15px;">Figure: Lipid-containing MCs transport lipids to tumor cells and NK cells via exosome-like vesicles. Inhibiting lipid transport by lipid-laden MCs through lysosomal pathway inhibitors abolishes metabolic reprogramming of tumor cells and NK cells, thereby reducing metastatic tumor colonization.</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;"><strong>Reference:</strong></span></p>
<p><span style="font-size: 15px;">Gong Z, Li Q, Shi J, Liu ET, Shultz LD, Ren G. Lipid-laden lung mesenchymal cells foster breast cancer metastasis via metabolic reprogramming of tumor cells and natural killer cells. Cell Metab. 2022;34(12):1960-1976.e9. doi:10.1016/j.cmet.2022.11.003</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;"><strong>Related Services:</strong></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/exosome-lipidomics-metabolomics-services.htm">Exosome Lipidomics &amp; Metabolomics Services</a></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/breast-cancer-targeted-exosome-modification-service.htm">Breast Cancer-Targeted Exosome Modification Service</a></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/lung-cancer-targeted-exosome-modification-service.htm">Lung Cancer-Targeted Exosome Modification Service</a></span></p>
<p>&nbsp;</p>
]]></content:encoded>
					
		
		
			</item>
		<item>
		<title>Ultrasensitive and Biomimetic 3D Recognition Technology for Visualizing Extracellular Vesicles with 2D Flexible Nanostructures</title>
		<link>https://www.creative-biolabs.com/blog/exosome/exosome-tech/ultrasensitive-and-biomimetic-3d-recognition-technology-for-visualizing-extracellular-vesicles-with-2d-flexible-nanostructures/</link>
		
		<dc:creator><![CDATA[biolabs]]></dc:creator>
		<pubDate>Fri, 28 Oct 2022 09:28:43 +0000</pubDate>
				<category><![CDATA[Exosome Tech]]></category>
		<guid isPermaLink="false">https://www.creative-biolabs.com/blog/exosome/?p=191</guid>

					<description><![CDATA[Extracellular vesicles (EVs)are a type of vesicle secreted by cells, characterized by a phospholipid bilayer structure. They carry a wealth of molecular information, including specific proteins, nucleic acids, lipids, and metabolites from<a class="moretag" href="https://www.creative-biolabs.com/blog/exosome/exosome-tech/ultrasensitive-and-biomimetic-3d-recognition-technology-for-visualizing-extracellular-vesicles-with-2d-flexible-nanostructures/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p><span style="font-size: 15px;">Extracellular vesicles (EVs)are a type of vesicle secreted by cells, characterized by a phospholipid bilayer structure. They carry a wealth of molecular information, including specific proteins, nucleic acids, lipids, and metabolites from the parent cell. Widely present in body fluids, EVs have emerged as crucial biomarkers for disease diagnosis and treatment evaluation in liquid biopsy technology. However, current methods for the rapid purification and detection of extracellular vesicles face challenges such as complex body fluid sample purification, tedious labeling steps, and difficulties in signal readout, indicating the need for further development.</span></p>
<p><span style="font-size: 15px;">Recently, Analytical Chemistry published a research paper titled &#8220;Biomimetic 3D Recognition with 2D Flexible Nanoarchitectures for Ultrasensitive and Visual Extracellular Vesicle Detection,&#8221; which was featured as the cover of the current issue.</span></p>
<p><img decoding="async" loading="lazy" class="size-full wp-image-192 aligncenter" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/01/1.png" alt="" width="742" height="308" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/01/1.png 742w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/01/1-300x125.png 300w" sizes="(max-width: 742px) 100vw, 742px" /></p>
<p><span style="font-size: 15px;">The research team introduced a high-affinity recognition and visual extracellular vesicle detection method named &#8220;HARVEST,&#8221; utilizing two-dimensional flexible Fe3O4-MoS2 nanostructures. Drawing inspiration from octopus predatory behavior, this method employs spatial recognition and multi-dental combination to biomimetically achieve three-dimensional recognition and capture of extracellular vesicles, significantly enhancing capture efficiency.</span></p>
<p><img decoding="async" loading="lazy" class="aligncenter  wp-image-194" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/01/2-1.jpg" alt="" width="346" height="459" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/01/2-1.jpg 711w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/01/2-1-226x300.jpg 226w" sizes="(max-width: 346px) 100vw, 346px" /></p>
<p><span style="font-size: 15px;">This work integrates two-dimensional flexible Fe3O4-MoS2 capture nanostructures with cholesterol lipid labeling chemistry, facilitating extracellular vesicle signal detection through the introduction of a fluorescence visualization system. Specifically, magnetic nanoparticles Fe3O4 and tumor marker aptamers are introduced into two-dimensional MoS2 for magnetic-specific capture of tumor-derived extracellular vesicles. Subsequently, HRP-cholesterol is anchored on the extracellular vesicle surface for lipid labeling, forming an HRP-EV complex. Within this complex, HRP catalyzes the decomposition of H2O2, causing an increase in fluorescence intensity of subsequently added H2O2-sensitive fluorescent quantum dots (QDs) as the concentration of HRP-EV rises. Further quantification of fluorescence values through smartphones enables the analysis of extracellular vesicle marker levels, converting biological signals into optical signals in the &#8220;extracellular vesicle-cholesterol-QD&#8221; system.</span></p>
<p><img decoding="async" loading="lazy" class="size-full wp-image-193 aligncenter" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/01/3-1.jpg" alt="" width="1000" height="633" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/01/3-1.jpg 1000w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/01/3-1-300x190.jpg 300w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/01/3-1-768x486.jpg 768w" sizes="(max-width: 1000px) 100vw, 1000px" /></p>
<p><span style="font-size: 15px;">This study establishes an efficient and convenient platform for the rapid enrichment and visual detection of extracellular vesicles. The high specific surface area and mechanical flexibility of aptamer-functionalized two-dimensional platforms enhance aptamer recognition, resulting in a higher capture rate of extracellular vesicles in a shorter time. This underscores its potential for sensitive and accurate detection of circulating biomarkers. In the current study, only the single extracellular vesicle marker CD44 was selected for clinical sample diagnosis. Subsequent detection can be expanded through the combination of multiple markers to further enhance diagnostic accuracy and broaden clinical applications.</span></p>
<p><span style="font-size: 15px;"><strong> </strong></span></p>
<p><span style="font-size: 15px;"><strong>Reference:</strong></span></p>
<p><span style="font-size: 15px;">Li Z, Ma D, Zhang Y, et al. Biomimetic 3D Recognition with 2D Flexible Nanoarchitectures for Ultrasensitive and Visual Extracellular Vesicle Detection. Anal Chem. 2022;94(42):14794-14800. doi:10.1021/acs.analchem.2c03839</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;"><strong>Related Services:</strong></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/exosomal-surface-markers-based-exosome-characterization.htm">Exosomal Surface Markers-based Exosome Characterization</a></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/exosome-labeling.htm">Exosome Labeling Services</a></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/exosome-manufacturing-services.htm">Exosome Manufacturing Services</a></span></p>
]]></content:encoded>
					
		
		
			</item>
		<item>
		<title>Comparison of the Use of Extracellular Vesicles and Circulating Tumor Cells in Liquid Biopsy</title>
		<link>https://www.creative-biolabs.com/blog/exosome/exosome-tech/comparison-of-the-use-of-extracellular-vesicles-and-circulating-tumor-cells-in-liquid-biopsy/</link>
		
		<dc:creator><![CDATA[biolabs]]></dc:creator>
		<pubDate>Sun, 28 Aug 2022 09:47:32 +0000</pubDate>
				<category><![CDATA[Exosome Tech]]></category>
		<guid isPermaLink="false">https://www.creative-biolabs.com/blog/exosome/?p=231</guid>

					<description><![CDATA[Traditional liquid biopsies for cancer primarily rely on the detection of  some recognized markers. However, during clinical use, many markers have limitations in statistical significance and robustness , leading to the removal<a class="moretag" href="https://www.creative-biolabs.com/blog/exosome/exosome-tech/comparison-of-the-use-of-extracellular-vesicles-and-circulating-tumor-cells-in-liquid-biopsy/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p><span style="font-size: 15px;">Traditional liquid biopsies for cancer primarily rely on the detection of  some recognized markers. However, during clinical use, many markers have limitations in statistical significance and robustness , leading to the removal of an increasing number of liquid biopsy biomarkers from cancer diagnosis or other related clinical guidelines. Researchers from the Copernicus University in Torun, Poland, published an article discussing that extracellular vesicles (EVs) and circulating tumor cells (CTCs) can be called true liquid biopsies. They compared the characterization, quantification, antigen information, downstream applications, and other aspects of EVs and CTCs, believing that they have complementary value in cancer diagnosis. This review, titled &#8220;Extracellular Vesicles and Circulating Tumor Cells &#8211; complementary liquid biopsies or standalone concepts?&#8221;, was published in the journal <em>Theranostics</em> on August 1.</span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/exosomal-rna-isolation-and-profiling.htm"><img decoding="async" loading="lazy" class=" wp-image-232 aligncenter" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/1-1.jpg" alt="" width="875" height="255" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/1-1.jpg 1232w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/1-1-300x88.jpg 300w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/1-1-1024x299.jpg 1024w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/1-1-768x224.jpg 768w" sizes="(max-width: 875px) 100vw, 875px" /></a></span></p>
<p><span style="font-size: 15px;">As early as 1966, Wichelhausen et al. published the earliest report on liquid biopsy, which obtained the patient&#8217;s cell tissue and was then further cultured and analyzed accordingly. In 1990, another important study showed that prostate-specific antigen (PSA) in serum samples correlated with prostate cancer tumor volume and differentiation and benign prostatic hyperplasia volume. A highly regarded and influential 1991 study in the New England Journal of Medicine established the gold standard for prostate cancer screening using PSA fluid. In 1994, the U.S. Food and Drug Administration approved PSA combined with a digital rectal examination (DRE) to detect prostate cancer. Another liquid biopsy cancer biomarker once thought to have the potential to take hepatocellular carcinoma (HCC) screening and diagnosis to another level is alpha-fetoprotein (AFP). This biomarker has even been recommended for inclusion in multiple international and national guidelines. Unfortunately, AFP has proven to be insensitive, as it is elevated in only 40-60% of HCC cases, especially early in the disease.</span></p>
<p><span style="font-size: 15px;">In addition to these two protein-based liquid biopsy cancer biomarkers, more liquid biopsy biomarkers for cancer have been developed subsequently. Especially in the past 15 years, &#8220;tumor circulation,&#8221; including circulating tumor cells (CTC), extracellular vesicles (EV), cell-free tumor DNA (ctDNA), cell-free DNA (cfDNA), circulating tumor RNA (ctRNA), and tumor-induced platelets (TEP), has  come into focus. All these biomarkers fall within the category of liquid biopsy or are considered part of precision medicine. In this review, researchers specifically discuss the differences and similarities between EVs and CTCs used as liquid biopsy tools, comprehensively outlining their limitations and advantages in cancer screening and diagnosis.</span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/exosomal-rna-isolation-and-profiling.htm"><img decoding="async" loading="lazy" class="aligncenter wp-image-233" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/2-1.jpg" alt="" width="624" height="316" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/2-1.jpg 600w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/2-1-300x152.jpg 300w" sizes="(max-width: 624px) 100vw, 624px" /></a></span></p>
<p><span style="font-size: 15px;">Researchers believe that in the case of cancer liquid biopsy, CTCs and EVs may be the most promising candidates for achieving powerful, high-sensitivity, and specific applications in the future. CTCs have been approved by the Food and Drug Administration for the diagnosis of certain types of solid cancers because CTCs are mainly derived from epithelial solid tumors with metastasis, while EVs are highly experimental markers that have not been fully developed and therefore hold great promise.</span></p>
<p><span style="font-size: 15px;">Researchers conducted an in-depth discussion and comparison of CTCs and EVs. Interestingly, both CTCs and EVs can be viewed as tools for tumor cells to fight against normal tissues in our body, but they are also tracers for cancer screening, diagnosis, and treatment monitoring. As shown in the figure below, the figure shows the independent capabilities of CTC and EV, which are not shared between the two. CTCs may be used in various ways as tumor-like components for testing drug sensitivity. EVs may be used for vectors for cancer treatment, which may be a promising vision that requires extensive research. EVs may also be used as cancer screening. Since during cancer evolution, cancer cells use EVs and CTCs to promote cancer survival and gain an advantage, we should also take advantage of CTCs and EVs and not just regard EVs and CTCs as simple biomarkers. Both EVs and CTCs orchestrate important oncogenic processes, but it appears that EVs are more involved in initiating carcinogenesis, whereas CTCs are generated later. However, both have the same goal: cancer evolution. So, which one is better for a liquid biopsy, EV, or CTC? This question is not important. For highly personalized medicine, or as the first step in early cancer screening, the real winner will be if it can help every cancer patient eliminate tumors and secondary diseases.</span></p>
<p><span style="font-size: 15px;">This review mainly describes the concepts of CTCs and EVs in an artistic comparative manner, highlighting and summarizing their differences in composition. It proposes several biomarkers for correlating CTCs and EVs with various cancers, demonstrating how they are applied as biomarkers in precision oncology and related downstream applications. For more details, readers are encouraged to refer to the original paper for reading.</span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/exosomal-rna-isolation-and-profiling.htm"><img decoding="async" loading="lazy" class="aligncenter wp-image-234" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/3.jpg" alt="" width="818" height="1064" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/3.jpg 754w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/3-231x300.jpg 231w" sizes="(max-width: 818px) 100vw, 818px" /></a></span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;"><strong>Reference:</strong></span></p>
<p><span style="font-size: 15px;">Słomka A, Wang B, Mocan T, et al. Extracellular Vesicles and Circulating Tumour Cells &#8211; complementary liquid biopsies or standalone concepts?. Theranostics. 2022;12(13):5836-5855. Published 2022 Aug 1. doi:10.7150/thno.73400</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;"><strong>Related Services:</strong></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/exosomal-cfdna-isolation-and-profiling.htm">Exosomal cfDNA Isolation and Profiling Service</a></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/exosomal-rna-isolation-and-profiling.htm">Exosomal RNA Isolation and qPCR Analysis Services</a></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/category-exosome-dna-extraction-kit-91.htm">Exosome DNA Extraction Kit</a></span></p>
]]></content:encoded>
					
		
		
			</item>
		<item>
		<title>Lncrna in Prostate Cancer: Intervention Pathways, Therapeutic Targets, and Exosome Markers</title>
		<link>https://www.creative-biolabs.com/blog/exosome/exosome-tech/lncrna-in-prostate-cancer-intervention-pathways-therapeutic-targets-and-exosome-markers/</link>
		
		<dc:creator><![CDATA[biolabs]]></dc:creator>
		<pubDate>Thu, 28 Jul 2022 09:53:28 +0000</pubDate>
				<category><![CDATA[Exosome Tech]]></category>
		<category><![CDATA[Exosome Therapy]]></category>
		<guid isPermaLink="false">https://www.creative-biolabs.com/blog/exosome/?p=237</guid>

					<description><![CDATA[Prostate cancer is one of the most malignant tumors in men and remains incurable due to its heterogeneous and progressive nature. Genetic and epigenetic changes play important roles in prostate cancer development.<a class="moretag" href="https://www.creative-biolabs.com/blog/exosome/exosome-tech/lncrna-in-prostate-cancer-intervention-pathways-therapeutic-targets-and-exosome-markers/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p><span style="font-size: 15px;">Prostate cancer is one of the most malignant tumors in men and remains incurable due to its heterogeneous and progressive nature. Genetic and epigenetic changes play important roles in prostate cancer development. A collaborative team from multiple research institutions including Islamic Azad University in Iran published a review in the journal <em>J Exp Clin Cancer Res</em>, emphasizing the role of epigenetic changes in the development of prostate cancer. The review also discussed the expression levels of long non-coding RNAs (lncRNAs) and their interactions with other signaling networks involved in prostate cancer, with a particular attention to the application of exosomal lncRNA as biomarkers for prostate cancer.</span></p>
<p><img decoding="async" loading="lazy" class="aligncenter wp-image-238" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/1-2.jpg" alt="" width="766" height="336" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/1-2.jpg 1057w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/1-2-300x131.jpg 300w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/1-2-1024x449.jpg 1024w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/1-2-768x336.jpg 768w" sizes="(max-width: 766px) 100vw, 766px" /></p>
<p><span style="font-size: 15px;">The prostate is a walnut-sized organ located in the pelvic region at the tail end of the bladder. The incidence of prostate cancer is high in males, with 1 in 7 men diagnosed in the United States, and globally, 1 in every 25 men is diagnosed with prostate cancer. Prostate enlargement that occurs with age is termed benign prostatic hyperplasia (BPH) and is associated with some symptoms observed in men over 60 years old, such as polyuria. Due to the histopathological and molecular similarities, BPH is considered a stage in the initiation of prostate tumor. However, the exact underlying mechanisms by which BPH leads to prostate tumor development are not fully understood. Prostate-specific antigen (PSA) testing is used for diagnosis, thus contributing to the higher incidence of prostate cancer in developed countries.</span></p>
<p><span style="font-size: 15px;">Prostate cancer is one of the malignant tumors in men. Newly released statistics show that compared with 2020, the incidence of prostate tumors has increased, with 248,530 new cases and 34,130 deaths. Due to advances in the medical field in recent years, especially in developed countries, the survival and prognosis of patients with prostate tumors have improved significantly. This can be observed in the 5-year survival rate of prostate tumor patients, which was 97.8% in 2016, significantly better compared to 66.9% in 1975. Age, race, heredity, family history, obesity, and smoking are the most common risk factors for the development of prostate tumors. If treatment for prostate cancer fails, a new form called castration-resistant prostate cancer (CRPC) develops, which is a problem in the clinical course. Some of the major genes mutated in CRPC prostate cancer include androgen receptor (AR), TP53, RB1, PTEN, and DNA damage repair (DDR).</span></p>
<p><span style="font-size: 15px;">There are many ways to treat prostate cancer. Surgery is beneficial in the initial stages of prostate cancer. For advanced and metastatic prostate cancer, chemotherapy and its combination with radiation therapy are used. In addition, androgen deprivation therapy (ADT) is widely used in the treatment of prostate cancer cells due to their dependence on androgens. Immunotherapy, including the use of immune checkpoint inhibitors, antibody-mediated radioimmunotherapy, antibody-drug conjugates, and bispecific antibodies, is a promising option in prostate cancer treatment. However, due to the aggressive nature of prostate cancer cells, they become resistant to different treatments and can activate pro-tumor signaling pathways to induce chemoresistance, radioresistance, ADT resistance, and immune resistance. Therefore, strategies should be sought to reverse treatment resistance in prostate tumors, and this goal is achieved through pharmacological and genetic interventions. Wnt, STAT3, Hedgehog (Hh), PTEN, PI3K/Akt, NF-κB, and SPOP are signaling networks that undergo aberrant expression in prostate cancer. Notably, noncoding RNAs (ncRNAs) have received special attention in prostate cancer because ncRNAs have dual roles in increasing or inhibiting tumor progression.</span></p>
<p><span style="font-size: 15px;">In this review, researchers describe in detail the functions of lncRNAs in prostate tumors. The study first introduces long non-coding RNAs (lncRNAs) and their biogenesis and biology, as well as their pathological functions. The researchers then specifically discuss the role of lncRNAs in the progression rate (growth and migration), chemoresistance, and radioresistance of prostate tumor cells. Furthermore, the role of lncRNAs as upstream mediators in regulating major molecular pathways in prostate cancer is also discussed. Finally, current applied therapies targeting lncRNAs in prostate cancer treatment are described.</span></p>
<p><span style="font-size: 15px;">The researchers believe that aberrant expression of lncRNAs in prostate cancer is well documented and that the rate of tumor cell progression is regulated by affecting molecular pathways such as STAT3, NF-κB, Wnt, PI3K/Akt, and PTEN. Furthermore, lncRNAs regulate the radiotherapy resistance and chemoresistance characteristics of prostate tumor cells. Overexpression of tumor-promoting lncRNAs such as HOXD-AS1 and CCAT1 can lead to drug resistance. In addition, lncRNAs can induce immune evasion in prostate cancer by upregulating PD-1. Pharmacological compounds such as quercetin and curcumin have been used to target lncRNAs. Furthermore, siRNA tools can reduce the expression of lncRNAs, thereby inhibiting prostate cancer progression. The prognosis and diagnosis of prostate tumors during the clinical course can be assessed by lncRNAs. Importantly, studying the expression levels of exosomal lncRNAs, such as lncRNA-p21, in the serum of prostate cancer patients can serve as reliable biomarkers.</span></p>
<p><img decoding="async" loading="lazy" class=" wp-image-239 aligncenter" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/2-2.jpg" alt="" width="826" height="432" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/2-2.jpg 1332w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/2-2-300x157.jpg 300w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/2-2-1024x535.jpg 1024w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/2-2-768x401.jpg 768w" sizes="(max-width: 826px) 100vw, 826px" /></p>
<p style="text-align: center;"><span style="font-size: 12px;"> Prostate Cancer Therapy Targeting lncRNA</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;"><strong>Exosomal lncRNA</strong></span></p>
<p><span style="font-size: 15px;">In recent years, special attention has been paid to extracellular vesicles (EVs) obtained from cancer and non-cancer cells. EVs are mainly divided into three categories, including exosomes, microvesicles, and apoptotic bodies, which play functional roles under physiological and pathological conditions. As nano-extracellular vesicles, exosomes exist in the TME, and various body fluids such as blood, saliva, pancreatic duct fluid, and amniotic fluid can participate in their transport to distant tissues and organs. Additionally, they also function through both autocrine and paracrine fluids. Exosomes provide communication between various cells, and they contain various macromolecules such as proteins, lipids, and, most importantly, nucleic acids. Exosomes originate from endosomal processing and are reported to contain ncRNAs, especially lncRNAs. Therefore, it is crucial to reveal the role of exosomal lncRNA in cancer.</span></p>
<p><span style="font-size: 15px;">It is worth mentioning that exosomal lncRNA can be used to distinguish prostate cancer from BPH. Therefore, by developing novel imaging methods for tracking exosomes, such as Antares2-mediated bioluminescence resonance energy transfer (BRET), a revolution in cancer diagnosis can be launched.</span></p>
<p><span style="font-size: 15px;">LncRNA is a potent regulator of different molecular pathways in prostate cancer, and microRNA (miRNA) is one of the most common downstream targets of lncRNA. An experiment showed that certain lncRNAs are enriched in prostate cancer exosomes, and lncRNAs that regulate miRNA expression are one of them. The exosomal lncRNAs ELAVL1 and RBMX are enriched in prostate cancer because of their ability to regulate the expression levels of miRNAs such as miRNA-17, miRNA-18a, miRNA-20a, miRNA-93, and miRNA-106b. Exosomes can accelerate the transfer of lncRNA to the extracellular environment, and based on the role of lncRNA as a tumor suppressor or tumorpromoting factor, it will affect the proliferation and invasion of prostate cancer cells. Although some studies have evaluated the role of exosomal lncRNA in prostate cancer, it seems that these types of lncRNA can be considered novel diagnostic and prognostic factors for prostate cancer, and their expression levels are important for distinguishing BPH and prostate cancer. Furthermore, more diagnostic tools should be developed to detect exosomes in prostate cancer.</span></p>
<p style="text-align: center;"><span style="font-size: 12px;">Table. An Overview of lncRNAs Involved in Prostate Cancer Progression/Inhibition</span><img decoding="async" loading="lazy" class="aligncenter wp-image-240" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/3-1.jpg" alt="" width="990" height="623" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/3-1.jpg 1624w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/3-1-300x189.jpg 300w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/3-1-1024x644.jpg 1024w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/3-1-768x483.jpg 768w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/02/3-1-1536x966.jpg 1536w" sizes="(max-width: 990px) 100vw, 990px" /></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;"><strong>Reference:</strong></span></p>
<p><span style="font-size: 15px;">Mirzaei S, Paskeh MDA, Okina E, et al. Molecular Landscape of LncRNAs in Prostate Cancer: A focus on pathways and therapeutic targets for intervention. J Exp Clin Cancer Res. 2022;41(1):214. Published 2022 Jul 1. doi:10.1186/s13046-022-02406-1</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;"><strong>Related Services:</strong></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/prostate-cancer-targeted-exosome-modification-service.htm">Prostate Cancer-Targeted Exosome Modification Service</a></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/exosomal-lncrna-microarray.htm">Exosomal LncRNA Microarray</a></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/exosomal-lncrna-sequencing.htm">Exosomal lncRNA Sequencing</a></span></p>
]]></content:encoded>
					
		
		
			</item>
		<item>
		<title>Analysis of Single Extracellular Vesicles for Early Cancer Detection</title>
		<link>https://www.creative-biolabs.com/blog/exosome/exosome-tech/analysis-of-single-extracellular-vesicles-for-early-cancer-detection/</link>
		
		<dc:creator><![CDATA[biolabs]]></dc:creator>
		<pubDate>Sat, 28 May 2022 03:32:35 +0000</pubDate>
				<category><![CDATA[Exosome Tech]]></category>
		<guid isPermaLink="false">https://www.creative-biolabs.com/blog/exosome/?p=299</guid>

					<description><![CDATA[Extracellular vesicles (EVs), actively secreted from cancer cells and host cells into the circulation, are emerging as one of the front-runners in diagnostics for early cancer detection, disease monitoring, and treatment evaluation.<a class="moretag" href="https://www.creative-biolabs.com/blog/exosome/exosome-tech/analysis-of-single-extracellular-vesicles-for-early-cancer-detection/">Read More...</a>]]></description>
										<content:encoded><![CDATA[<p><span style="font-size: 15px;">Extracellular vesicles (EVs), actively secreted from cancer cells and host cells into the circulation, are emerging as one of the front-runners in diagnostics for early cancer detection, disease monitoring, and treatment evaluation. Researchers from the Center for Systems Biology at Massachusetts General Hospital published a review in the journal Trends in Molecular Medicine, outlining EVs and the basic principles for early cancer detection, studying emerging technologies for single EV analysis and their application in early cancer detection.</span></p>
<p><img decoding="async" loading="lazy" class="aligncenter wp-image-300" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/04/1-1.jpg" alt="" width="748" height="415" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/04/1-1.jpg 2013w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/04/1-1-300x166.jpg 300w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/04/1-1-1024x568.jpg 1024w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/04/1-1-768x426.jpg 768w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/04/1-1-1536x852.jpg 1536w" sizes="(max-width: 748px) 100vw, 748px" /></p>
<p><span style="font-size: 15px;">​​Does someone have cancer that will grow malignantly and eventually metastasize? This is a critical question that the medical community, including medicine, oncology, preventive medicine, medical epidemiology, and health care cost communities, have been grappling with. It is known that growing cancer releases a variety of components into the circulation, including whole cells (i.e., circulating tumor cells (CTCs)), tumor-derived DNA (ctDNA), various EVs, proteins, and metabolites. The premise of &#8220;liquid biopsy&#8221; is to use these components derived from tumor cells to make a diagnosis without relying on medical imaging or tumor biopsies. Currently, key questions in early cancer diagnosis are: Which blood component is best to detect? How common is a given marker (rare or ultra-rare)? And how specific is that marker for a given cancer type?</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;">EVs have emerged as leaders in early cancer detection, disease monitoring, and treatment evaluation. One advantage of EVs is their continuous shedding by dividing tumor cells, with indications suggesting a correlation between higher tumor metabolic rates and increased EV production. Unlike ctDNA diagnostics, EV shedding occurs in living cells and is not rely on tumor cell death. Therefore, EV production likely serves as an ongoing event and represents one of the earliest sources of biomarkers in cancer cells. In advanced melanoma, the DNA of mutant alleles BRAFV600E and cKITD816V was found not to be associated with EVs. However, the authors believe this discrepancy may not hold true in patients with early-stage cancer. Direct comparisons between exosomal DNA and ctDNA in other studies have revealed that exosomal DNA is superior to ctDNA in detecting mutations in pancreatic and lung cancer. Furthermore, EVs address a significant issue that has hindered the wider use of RNA and proteins by protecting cargo from degradation in the bloodstream. Additionally, EVs can encapsulate multiple cargoes within vesicles, ultimately indicating the tissue of origin.</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;">Recent studies have demonstrated that circulating tumor-derived EVs (ctEVs) are heterogeneous, with only a minority carrying tumor-specific biomarkers such as mutant proteins. Detecting of these highly specific but rare ctEVs among a large population of host cell-derived EVs may require single EV analysis (sEVA). This review highlights recent advances in sEVA, focusing on clinical applications, discussing current limitations, and proposing further work needed to enhance existing and emerging toolkits.</span></p>
<p style="text-align: center;"><img decoding="async" loading="lazy" class=" wp-image-301 aligncenter" src="http://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/04/2-1.jpg" alt="" width="777" height="369" srcset="https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/04/2-1.jpg 1871w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/04/2-1-300x142.jpg 300w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/04/2-1-1024x486.jpg 1024w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/04/2-1-768x365.jpg 768w, https://www.creative-biolabs.com/blog/exosome/wp-content/uploads/sites/7/2024/04/2-1-1536x729.jpg 1536w" sizes="(max-width: 777px) 100vw, 777px" /><span style="font-size: 12px;">Figure 1. Summary of Individual EV Detection Methods</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;">The authors mentioned that mutated KRAS protein, mutated P53 and other biomarkers were present in approximately 3% of EVs in patients with advanced pancreatic cancer and only 0.01% of EVs in patients with early-stage cancer. A clinical study indicated that current sEVA methods could detect approximately 90% of patients with stage 1 PDAC. With the ongoing development and advancement of clinically feasible single EV detection technologies, we are gaining a deeper understanding of the scarcity and complexity of ctEVs. Several questions are actively being explored: (i)How can existing single EV technologies be made more sensitive? (ii) Can multiplexing strategies be developed to interrogate ctEV to identify their organ of origin (to find small cancers in the human body); (iii)Is it possible to identify and differentiate ctEVs from relatively indolent (tumors doubling in years) versus highly aggressive (tumors doubling in months) cancers? We expect that the sensitivity of sEVA will increase with the emergence of improved antibodies against key targets in the future. Areas for improvement include more efficient pre-analysis techniques to prevent the loss of rare ctEVs, integration of sEVA with microfluidics, and enhancement of optical systems. Although methods like digital droplet PCR (ddPCR) and ddEV-seq have been developed, they are complex, time-consuming, and require further optimization. Another approach involves cycle imaging of different EV targets, such as using four channels (488 nm, 535 nm, 594 nm, 647 nm) imaged over five cycles to assess 20 biomarkers in a single EV.</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;">Another area of significant clinical interest is combining of sEVA with cross-sectional imaging to achieve: (i) spatial localization of targets; (ii)temporal information provision; and (iii) improved differential diagnosis capabilities. Current diagnostic tools are lacking in effectively stratifying patients for the most suitable treatment, avoiding treatment-related toxicities, and achieving cost-effectiveness. Dynamic contrast-enhanced functional CT imaging (DCE-CT) is generally insufficient in this regard. sEVA holds promise in revolutionizing existing imaging methods by integrating EV biomarkers to enhance treatment monitoring and clinical decision-making, although substantial work remains in this area.</span></p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;">In summary, sEVA represents a promising frontier in research that will elucidate the biology of circulating EVs and, hopefully, facilitate the emergence of clinical trials for early detection across various malignancies.</span></p>
<p>&nbsp;</p>
<p>&nbsp;</p>
<p><span style="font-size: 15px;"><strong>Reference</strong><strong>:</strong></span></p>
<p><span style="font-size: 12px;">Ferguson S, Yang KS, Weissleder R. Single extracellular vesicle analysis for early cancer detection. Trends Mol Med. 2022 Aug;28(8):681-692. doi: 10.1016/j.molmed.2022.05.003. Epub 2022 May 24. PMID: 35624008; PMCID: PMC9339504.</span></p>
<p><span style="font-size: 15px;"><strong>Related Services:</strong></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/single-cell-exosome-combined-research-services.htm">Single-Cell &amp; Exosome Combined Research Services</a></span></p>
<p><span style="font-size: 15px;"><a href="https://www.creative-biolabs.com/exosome/exosome-ngs-rna-next-gengeration-sequencing.htm">Exosome &#8211; NGS (RNA Next Gengeration Sequencing)</a></span></p>
]]></content:encoded>
					
		
		
			</item>
	</channel>
</rss>