Advantages of Aptamer in Oncology Therapy
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Aptamers are a group of single-stranded DNA or RNA oligonucleotides with a length of 15-100 nt and a molecular weight of 5-30 kDa. Structurally, the DNA or RNA oligonucleotides can be folded into complex tertiary or quadruplex structures.
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Aptamers are structurally stable and can be stored for a long time. They can withstand a broad range of temperatures.
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Aptamers, like antibodies, specifically bind to a variety of biological substances such as proteins, carbohydrates, small molecules, toxins, and even whole cells. Aptamers can be developed as a class of targeting ligands for therapeutic applications.
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Aptamers are synthesized in a cell-free system, which allows rapid and low-cost bulk production with a minimal batch-to-batch variation.
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Aptamers can be chemically modified on their specific site. Some modifications on aptamers' sugar, base, and phosphate backbone increase their nuclease resistance and binding affinity.
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Some drugs, siRNA, and nanoparticles can be conjugated to aptamers, which broaden the therapeutic applications of aptamers.
Aptamers in Tumor Therapy
Owing to the above advantages, aptamers can be developed as a potent therapeutics for tumor treatment. On the one hand, aptamers have the potential to be used as targeting ligands for cancer treatment. Aptamers targeting specific cancer cells can advance targeted delivery of a wide range of therapeutic agents, including antibodies, toxins, siRNAs, and aptamers. Yu et al. (2020) have reported a novel targeted drug delivery system (TDDS) which is established by loading docetaxel in albumin nanoparticles that are conjugated to nucleolin-targeted aptamers. The TDDS significantly increased the killing of CT26 colon cancer cells, providing a potential therapeutics for targeted treatment of colon cancer. On the other hand, aptamers can be developed as inhibitors to block some important proteins or receptor-ligand binding that is critical for cancer development. For example, anti-VEGF aptamers have been shown to inhibit VEGF-associated tumor vessel formation by blocking the VEGF/VEGF-R interaction. Aptamers targeting PD-1/PD-L1 (e.g., PEG-MP7) were shown to reduce tumor growth and increase survival in mouse tumor models. Aptamers targeting CXCL12 (e.g., NOX-A12) were shown to suppress angiogenesis and tumor cell proliferation, invasion, and metastasis by inhibiting CXCL12-CXCR4/CXCR7 interactions.
Fig. 1 Aptamers targeting coagulation factors.1, 2
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References
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Morita, Yoshihiro, et al. "Aptamer therapeutics in cancer: current and future." Cancers 10.3 (2018): 80.
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under Open Access license CC BY 4.0, without modification
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Questions & Answer
A: Aptamers have shown promise in several areas of oncology research. They can be used for targeted cancer imaging, allowing precise visualization of tumors in diagnostic imaging techniques. Aptamers are also being explored as therapeutic agents themselves, including as inhibitors of cancer-promoting proteins or as components of immunotherapies. Additionally, aptamers have potential applications in early cancer detection, monitoring treatment response, and predicting patient outcomes.
A: Targeting intracellular proteins with aptamers is challenging since they need to bypass the cellular membrane. To overcome this, a technique called cell-SELEX is used, where aptamers are selected against intact cancer cells. This approach allows the aptamers to access and bind to intracellular targets, enabling the development of aptamer-based therapies against intracellular proteins involved in cancer progression.
A: Aptamers and small molecule inhibitors are both used in cancer therapy, but they differ in their mechanisms of action and target specificity. Small molecule inhibitors typically target enzymatic or signaling pathways involved in cancer cell proliferation. In contrast, aptamers can target specific proteins, receptors, or cells with high specificity. Aptamers offer advantages such as modifiability, potential for multi-targeting, and reduced off-target effects compared to small molecules.
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