Targeting Lysosome

Delivery systems constructed by utilizing specific targeting module mainly small molecules like peptide, heterocyclics, oligonucleotides have been widely demonstrated by many research groups. Lysosomal delivery is reported to be one of the potential approach for cancer treatment. Having worked in the field of targeted delivery for many years, Creative Biolabs has developed innovative and diversified module delivery systems, and provides a wide range of targeted delivery services for lysosomal to promote your project.

Lysosome

The Lysosomes are single membranous, subcellular organelles involved in macromolecule turnover. They have an acidic pH within their lumen and approximately 60 hydrolases capable of degrading various biological macromolecules. Cargo reaches the lysosome through various pathways: endogenously via autophagy, and exogenously via phagosomes or endosomes. To date, approximately 50 monogenic diseases are primarily associated with lysosomes, of which the majority fall within the category of lysosomal storage diseases. Any disruption of lysosomal function can lead to an accumulation of undegraded substrates in lysosomes, eventually compromising cellular function. Niemann-Pick disease, Hurler syndrome, Pompe disease, etc., are a few examples arising due to such disruption. Besides lysosomal storage diseases, lysosomes have also been linked to Alzheimer’s, autoimmune diseases, and resistance to autoimmune diseases.

Fig.1 Overview of lysosomal function.¹

Lysosomal Targeting

Primarily, in order to achieve targeting delivery of a molecule to the lysosomes, module targeting receptors expressed on the cell surface like transferrin, folate, vascular endothelial growth factor, and low-density lipoproteins are normally used. Lysosomes contain soluble and transmembrane proteins, which are targeted to lysosomes after their synthesis in the cytoplasm. Researchs showed that the main targeting signal for proteins destined for the lysosomes is mannose-6-phosphate.

Fig.2 Multifunctional TPP-PEG-biotin self-assembled nanoparticle drug delivery-based combination therapeutic approach for co-targeting of GRP78 and lysosome.²

There are basically two classes of motifs for targeting to lysosomes: tyrosine-based and dileucine-based sorting signals. The tyrosine-based motif has consensus sequence YXXφT where X is any amino acid and φ is amino acid with bulky hydrophobic side chain. The dileucine-based motif has either [DE]XXXL[LI] or a DXXLL pattern, which targets cargo to lysosomes, where square brackets indicate alternatives. Insulin-like growth factor II-β-glucuronidase was shown to be delivered with the aid of the insulin-like growth factor II/mannose 6-phosphate receptor and use of Tat-β-glucuronidase was used for uptake by absorptive endocytosis followed by delivery into the lysosomes.

What Can We Do for You?

Equipped with our well-established module delivery systems, we can provide either individual targeting module or different kind of module-payload/carrier conjugates targeting lysosome.

Features of Our Services:

• Good stability in the bloodstream
• Efficiently avoid the nonspecific uptake by normal cells
• Readily penetrate the cell membrane barrier
• Readily escape from the cytoplasm
• Different combinational strategy

Creative Biolabs is capable to provide the largest and diversiform portfolio of lysosomal delivery services. Our proven and optimized platforms can help you quickly get satisfactory results. In addition, we can also provide custom services based on your requirements. Please contact us for more information.

References

1. Jin, Jun, et al. "Lysosomes in T Cell Immunity and Aging." Frontiers in aging 2 (2021): 809539.
2. Purushothaman, Baskaran, et al. "Multifunctional TPP-PEG-biotin self-assembled nanoparticle drug delivery-based combination therapeutic approach for co-targeting of GRP78 and lysosome." Journal of Nanobiotechnology 18.1 (2020): 1-19.

Our services are For Research Use Only. We do not provide services to individuals.