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Exosome-mediated Let7c-5p Delivery for Breast Cancer Therapeutic Development
Biotechnology and Bioprocess Engineering ( IF 2.5 ) Pub Date : 2020-08-05 , DOI: 10.1007/s12257-020-0002-0
Haneul Kim , Won Jong Rhee

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.



中文翻译:

外来体介导的Let7c-5p的乳腺癌治疗发展。

乳腺癌是全世界女性的第二大死亡原因。尽管已经开发了化学或生物药物,但是它们的治疗效果有限。为了克服这个问题,已经开发了基于核酸药物的替代治疗剂。在几种基于核酸的药物中,已知微小RNA(miRNA)在癌细胞中会急剧下调,这赋予癌细胞某些功能,例如过度增殖。为了调节这些癌症相关的miRNA,包括癌细胞中的let7c-5p,可以通过补充miRNA模拟物来上调癌细胞中低水平的抑制癌症的miRNA。但是,由于miRNA不稳定,因此需要特定的运输工具才能有效且安全地进行运输。外泌体是来源于细胞的纳米级细胞外载体。由于外泌体包含各种生物分子,并且容易被细胞摄取,因此它们被认为毒性较小,不适合用作miRNA传递载体。因此,已经开发了HEK293T细胞来源的外来体作为let7c-5p的递送载体用于乳腺癌治疗。为了实现有效的传递,外泌体中加载了let7c-5p,然后成功地传递到了MDA-MB-231乳腺癌细胞中。已发现当用载有let7c-5p的外来体处理细胞时,癌细胞的增殖和迁移被显着抑制。分析了乳腺癌细胞中let7c-5p的下游靶标,以证明let7c-5p由外来体递送,释放并与其靶标mRNA杂交以发挥其抗癌活性。总体,

更新日期:2020-08-05
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