Balaraman Ashok Kumar, Arockia Babu M, Afzal Muhammad, Sanghvi Gaurav, M M Rekha, Gupta Sofia, Rana Mohit, Ali Haider, Goyal Kavita, Subramaniyan Vetriselvan, Wong Ling Shing, Kumarasamy Vinoth
Research and Enterprise, University of Cyberjaya, Persiaran Bestari, Cyber 11, Cyberjaya, Selangor, 63000, Malaysia.
Institute of Pharmaceutical Research, GLA UNIVERSITY, Mathura, UP, 281406, India.
Regen Ther. 2025 Feb 13;28:558-572. doi: 10.1016/j.reth.2025.01.019. eCollection 2025 Mar.
Recently, increasing interest has been in utilizing mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), especially exosomes, as nanocarriers for miRNA delivery in cancer treatment. Due to such characteristics, nanocarriers are specific: biocompatible, low immunogenicity, and capable of spontaneous tumor accumulation. MSC-EVs were loaded with therapeutic miRNAs and minimized their susceptibility to degradation by protecting the miRNA from accessibility to degrading enzymes and providing targeted delivery of the miRNAs to the tumor cells to modulate oncogenic pathways. In vitro and in vivo experiments suggest that MSC-EVs loaded with miRNAs may inhibit tumor growth, prevent metastasis, and increase the effectiveness of chemotherapy and radiotherapy. However, these improvements present difficulties such as isolation, scalability, and stability of delivered miRNA during storage. Furthermore, the issues related to off-target effects, as well as immunogenicity, can be a focus. The mechanisms of miRNA loading into MSC-EVs, as well as their targeting efficiency and therapeutic potential, can be outlined in this manuscript. For the final part of the manuscript, the current advances in MSC-EV engineering and potential strategies for clinical application have been described. The findings of MSC-EVs imply that they present MSC-EVs as a second-generation tool for precise oncology.
最近，人们越来越关注利用间充质干细胞衍生的细胞外囊泡（MSC-EVs），尤其是外泌体，作为癌症治疗中miRNA递送的纳米载体。由于这些特性，纳米载体具有特异性：生物相容性好、免疫原性低，并且能够自发地在肿瘤中积累。将治疗性miRNA装载到MSC-EVs中，并通过保护miRNA不被降解酶作用以及将miRNA靶向递送至肿瘤细胞以调节致癌途径，从而降低其降解敏感性。体外和体内实验表明，装载有miRNA的MSC-EVs可能抑制肿瘤生长、防止转移，并提高化疗和放疗的效果。然而，这些改进存在一些困难，如所递送miRNA的分离、可扩展性以及储存期间的稳定性。此外，与脱靶效应以及免疫原性相关的问题可能成为关注焦点。本手稿将概述miRNA装载到MSC-EVs中的机制及其靶向效率和治疗潜力。在手稿的最后部分，描述了MSC-EV工程的当前进展以及临床应用的潜在策略。MSC-EVs的研究结果表明，它们将MSC-EVs作为精准肿瘤学的第二代工具。
