CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Exosome-based miRNA delivery: Transforming cancer treatment with mesenchymal stem cells.
Exosome-based miRNA delivery: Transforming cancer treatment with mesenchymal stem cells.
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近年来,利用间充质干细胞来源的细胞外囊泡(MSC-EVs),尤其是外泌体,作为miRNA递送的纳米载体用于癌症治疗引起了越来越多的关注。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蓄积。MSC-EVs被装载以治疗性miRNA,并通过保护miRNA免受降解酶的作用,以及将miRNA靶向递送至肿瘤细胞以调节致癌通路,从而最大限度地降低其被降解的易感性。体外和体内实验表明,装载miRNA的MSC-EVs可能抑制肿瘤生长、预防转移,并提高化疗和放疗的有效性。
然而,这些改进也带来了困难,例如递送miRNA在储存期间的分离、可扩展性和稳定性问题。此外,脱靶效应以及免疫原性相关问题也可能成为关注焦点。本文概述了miRNA装载到MSC-EVs中的机制,以及它们的靶向效率和治疗潜力。在本文的最后部分,描述了MSC-EV工程的当前进展和临床应用的潜在策略。MSC-EVs的研究结果表明,它们将MSC-EVs呈现为精准肿瘤学的第二代工具。
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.
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