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KMID : 1094720200250040513
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Biotechnology and Bioprocess Engineering
2020 Volume.25 No. 4 p.513 ~ p.520
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Exosome-mediated Let7c-5p Delivery for Breast Cancer Therapeutic Development
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Kim Ha-Neul
Rhee Won-Jong
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Abstract
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Breast cancer is the second leading cause of death among women worldwide. Although chemical or biological drugs have been developed, they have limited therapeutic effects. To overcome this issue, alternative therapeutic agents based on nucleic acid drugs have been developed. Of the several nucleic acid-based drugs, micro-RNAs (miRNAs) are known to be drastically downregulated in cancer cells, and this endows cancer cells with certain abilities such as hyper-proliferation. To regulate these cancer-related miRNAs, including let7c-5p in cancer cells, low levels of cancer-inhibiting miRNAs in cancer cells can be upregulated by supplementing miRNA mimics. However, because miRNAs are unstable, a specific delivery vehicle is required for their efficient and safe delivery. Exosomes are nano-sized extracellular vehicles derived from cells. Because exosomes contain various biomolecules and are easily uptaken by cells, they are considered to be less toxic and less suitable as miRNA delivery vehicles. Accordingly, HEK293T cell-derived exosomes have been developed as delivery vehicles of let7c-5p for breast cancer treatment. To achieve effective delivery, exosomes were loaded with let7c-5p and then successfully delivered to MDA-MB-231 breast cancer cells. It was found that cancer cell proliferation and migration were significantly suppressed when cells were treated with let7c-5p-loaded exosomes. Downstream targets of let7c-5p in breast cancer cells were analyzed to demonstrate that let7c-5p was delivered by exosomes, released, and hybridized with its target mRNAs to exert its anti-cancer activity. Overall, human exosome-based let7c-5p delivery is a potential anti-cancer drug and can contribute to the development of highly effective breast cancer therapy.
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KEYWORD
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breast cancer, exosome, miRNA, let7c-5p, drug delivery system
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