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载 miR-21 反义 RNA 纳米粒的制备、表征及其体外抑瘤作用

Preparation, characterization, and in vitro tumor-suppressive effect of anti-miR-21-equipped RNA nanoparticles.

机构信息

Department of Urology, Joint Centre of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325035, PR China; Engineering Research Center of Clinical Functional Materials and Diagnosis & Treatment Devices of Zhejiang Province, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang Province, 325011, PR China.

Engineering Research Center of Clinical Functional Materials and Diagnosis & Treatment Devices of Zhejiang Province, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang Province, 325011, PR China; School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian Province, 361102, PR China.

出版信息

Biochem Biophys Res Commun. 2021 Jun 18;558:107-113. doi: 10.1016/j.bbrc.2021.04.040. Epub 2021 Apr 24.

DOI:10.1016/j.bbrc.2021.04.040
PMID:33906109
Abstract

MicroRNAs play an irreplaceable role in gene expression regulation. Upregulation of several miRNAs increases the risk of invasion and metastasis of breast cancer cells. An oncogenic miRNA, miR-21, is highly expressed in triple-negative breast cancer (TNBC) and is associated with tumor proliferation, invasion, carcinogenesis, prognosis, and therapeutic resistance. However, targeted delivery of therapeutic anti-miRNAs into cancer cells remains challenging, especially for TNBC. In this study, we report the application of an RNA nanotechnology-based platform for the targeted delivery of anti-miR-21 by epidermal growth factor receptor (EGFR) aptamer in vitro to TNBC and chemical-resistant breast cancer cells. RNA nanoparticles reduced cell viability and sensitized breast cancer cells to doxorubicin (DOX) treatment in vitro. Inhibition of miR-21 by RNA nanoparticles suppressed TNBC cell invasion, migration, and colony formation. The results indicate the potential application of nanotechnology-based delivery platforms in clinical anti-cancer therapeutics.

摘要

微小 RNA 在基因表达调控中发挥着不可替代的作用。几种 miRNA 的上调增加了乳腺癌细胞侵袭和转移的风险。致癌 miRNA,miR-21,在三阴性乳腺癌(TNBC)中高表达,与肿瘤增殖、侵袭、癌变、预后和治疗耐药性有关。然而,将治疗性抗 miRNA 靶向递送到癌细胞中仍然具有挑战性,特别是对于 TNBC。在这项研究中,我们报告了一种基于 RNA 纳米技术的平台在体外靶向递送 EGFR 适体抗 miR-21 的应用,用于 TNBC 和化学抗性乳腺癌细胞。RNA 纳米颗粒降低了细胞活力,并使乳腺癌细胞对阿霉素(DOX)治疗敏感。RNA 纳米颗粒抑制 miR-21 抑制了 TNBC 细胞的侵袭、迁移和集落形成。结果表明,基于纳米技术的递药平台在临床抗癌治疗中有应用潜力。

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