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.
我们的工作确立了CD81作为连接放射抵抗与免疫逃逸的关键桥梁,其通过维持GBM中CD274的丰度发挥作用,并突显CD81作为优化放射免疫治疗的有前景的治疗靶点。
英文原题:Cell-Driven Encapsulation of Chlorophyllin-Based Carbon Dots within Exosomes for Enhanced Photodynamic Therapy: miRNA Profiling Reveals Mechanistic Insights.
外泌体,即纳米级细胞外囊泡,因其能够绕过生物屏障、低毒性、高稳定性以及固有的靶向能力,已成为药物递送中前景广阔的载体。
外泌体作为纳米级细胞外囊泡,因其能够绕过生物屏障、低毒性、高稳定性以及固有的靶向能力,已成为药物递送中颇具前景的载体。间充质干细胞来源的外泌体(EXO MSC)因其对肿瘤微环境的天然趋向性,为增强治疗性货物递送提供了理想平台。在本研究中,我们展示了一种方法,即通过细胞驱动的摄取机制将红光发射的叶绿素基碳点(Chl-CDs)封装在 EXO MSC 内,形成 CD@EXO MSC。这些外泌体实现了更优越的光动力治疗(PDT)疗效,与游离的 Chl-CDs 相比,所需纳米材料少 40 倍。来自胶质母细胞瘤细胞 miRNA 谱的机制性见解表明,增强的疗效是由外排转运蛋白基因、氧化应激反应和内吞途径的调控所介导的。这项工作凸显了将光敏剂与富含 miRNA 的外泌体相结合以实现靶向且持续的治疗性递送的协同潜力,为癌症治疗中的多层面方法铺平了道路。
Exosomes, nanoscale extracellular vesicles, have emerged as promising carriers in drug delivery due to their ability to bypass biological barriers, low toxicity, high stability, and intrinsic targeting capabilities. Mesenchymal stem-cell-derived exosomes (EXO MSC ), with their natural tropism toward the tumor microenvironment, offer an ideal platform for enhancing therapeutic cargo delivery. In this study, we demonstrate an approach where red-emission chlorophyll-based carbon dots (Chl-CDs) were encapsulated within EXO MSC through a cell-driven uptake mechanism, creating CD@EXO MSC . These exosomes achieved superior photodynamic therapy (PDT) efficacy, requiring 40 times less nanomaterial compared to freestanding Chl-CDs. Mechanistic insights from glioblastoma cell miRNA profiling revealed that the enhanced efficacy was mediated by the regulation of efflux transporter genes, oxidative stress responses, and endocytosis pathways. This work highlights the synergistic potential of combining photosensitizers and miRNA-rich exosomes to achieve targeted and sustained therapeutic delivery, paving the way for a multifaceted approach in cancer therapy.
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