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:Engineered mesenchymal stem cell-derived exosomes with high CXCR4 levels for targeted siRNA gene therapy against cancer.
Engineered mesenchymal stem cell-derived exosomes with high CXCR4 levels for targeted siRNA gene therapy against cancer.
基因治疗已被用于多种疾病,并显示出显著的抗癌或抑癌效果。
基因治疗已被用于多种疾病,并显示出显著的抗癌或抑癌效果。基因治疗正逐渐发展成为肿瘤治疗领域最引人注目的前沿热点。目前用于基因治疗的载体安全性和递送效率较差,因此迫切需要开发新型基因治疗递送载体。由于外泌体具有优异的稳定性和生物安全性,其作为新型核酸治疗药物载体的应用正在如火如荼地开展,展现出巨大的临床应用前景。间充质干细胞(MSCs)具有天然的归巢特性,可自发聚集于损伤部位、炎症部位甚至肿瘤部位。这一特性归因于其表面表达的多种趋向性因子;例如,CXC趋化因子受体4型(CXCR4)可与肿瘤表面高表达的基质细胞衍生因子-1(SDF-1)特异性结合,这对于MSCs在肿瘤部位的聚集至关重要。本研究中所使用的间充质干细胞经过基因工程改造,以获得高表达CXCR4的外泌体作为靶向基因药物递送载体,随后通过电转化加载Survivin基因,构建全新的基因药物递送系统(CXCR4 high Exo/si-Survivin)。最后,进行了相关的体内和体外实验。我们观察到,该新型递送系统能够高效聚集于肿瘤部位并将siRNA释放到肿瘤细胞中,在体内敲低肿瘤细胞中的Survivin基因,从而抑制肿瘤生长。这种新型基因药物递送系统具有巨大的临床转化价值,为肿瘤的临床治疗提供了新策略。
Gene therapy has been used in a variety of diseases and shows brilliant anticancer or cancer suppression effects. Gene therapy is gradually evolving as the most compelling frontier hotspot in the field of cancer therapy. The current vehicles used in gene therapy have poor safety and low delivery efficiency, and thus, it is urgent to develop novel delivery vehicles for gene therapy. Due to the excellent stability and biosafety of exosomes, their use as drug carriers for novel nucleic acid therapy is in full swing, revealing huge prospects for clinical application. Mesenchymal stem cells (MSCs) have a natural homing property and can spontaneously accumulate at injury sites, inflammation sites, and even tumour sites. This feature is attributed to a variety of tropism factors expressed on their surface; for example, CXC chemokine receptor type 4 (CXCR4) can specifically bind to the highly expressed stromal cell derived factor-1 (SDF-1) on the tumour surface, which is essential for accumulation of MSCs at the tumour site. The mesenchymal stem cells used in this study were genetically engineered to obtain exosomes with high CXCR4 expression as carriers for targeted gene-drug delivery, and then, the Survivin gene was loaded via electrotransformation to construct a brand-new gene-drug delivery system (CXCR4 high Exo/si-Survivin). Finally, related in vivo and in vitro experiments were conducted. We observed that the new delivery system can efficiently aggregate at the tumour site and release siRNA into tumour cells, knocking down the Survivin gene in tumour cells in vivo and thereby inhibiting tumour growth. This new gene-drug delivery system has tremendous clinical transformation value and provides a new strategy for clinical treatment of tumours.
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