Anticancer effect of hUC-MSC-derived exosome-mediated delivery of PMO-miR-146b-5p in colorectal cancer

作者：Siming Yu, Ran Liao, Lu Bai, Madi Guo, Y. Zhang, Yumin Zhang, Qi Yang, Yushuai Song, Zhiwei Li, Qingwei Meng, Shubin Wang, Xiaoyi Huang · 发表于：Drug Delivery and Translational Research · 年份：2023 · DOI：10.1007/s13346-023-01469-7 · 被引用次数：25 · 研究领域：Extracellular vesicles in disease、MicroRNA in disease regulation、RNA Interference and Gene Delivery

Abstract Antisense oligonucleotide (ASO) is a novel therapeutic platform for targeted cancer therapy. Previously, we have demonstrated that miR-146b-5p plays an important role in colorectal cancer progression. However, a safe and effective strategy for delivery of an ASO to its targeted RNA remains as a major hurdle in translational advances. Human umbilical cord mesenchymal cell (hUC-MSC)–derived exosomes were used as vehicles to deliver an anti-miR-146b-5p ASO (PMO-146b). PMO-146b was assembled onto the surface of exosomes (e) through covalent conjugation to an anchor peptide CP05 (P) that recognized an exosomal surface marker, CD63, forming a complex named ePPMO-146b. After ePPMO-146b treatment, cell proliferation, uptake ability, and migration assays were performed, and epithelial-mesenchymal transition progression was evaluated in vitro. A mouse xenograft model was used to determine the antitumor effect and distribution of ePPMO-146b in vivo. ePPMO-146b was taken up by SW620 cells and effectively inhibited cell proliferation and migration . The conjugate also exerted antitumor efficacy in a xenograft mouse model of colon cancer by systematic administration, where PPMO-146b was enriched in tumor tissue. Our study highlights the potential of hUC-MSC-derived exosomes anchored with PPMO-146b as a novel safe and effective approach for PMO backboned ASO delivery. Graphical Abstract Schematic illustration of the preparation of an exosomal anchor peptide (CP05)-PMO that conjugat...