线粒体与siRNA共递送体系用于肿瘤多药耐药性逆转的应用研究

Malignancy is one of the most serious threats to human health and chemotherapy is an important treatment in clinical practices. Unfortunately, the chemotherapeutic effects are greatly limited by multidrug resistance (MDR). According to recent study, the mechanism of MDR can be divided into “pump-related” and “pump-unrelated” pathways. The “pump-related” pathway is mainly caused by overexpression of ATP-binding cassette (ABC) transporters, which significantly pump drugs out of cancer cells, thus reducing intracellular drug accumulation. The “pump-unrelated” mechanism is a kind of intracellular ant-apoptotic pathway, which is related to the mitochondrion dysfunction. In this study, we aim to develop a new mitochondrion-siRNA complex to co-deliver health mitochondrion and functional siRNA into resistant cancer cells, which can inhibit drug efflux by siRNA, and activate intracellular apoptotic signals by health mitochondrion. In this way, “pump-related” and “pump-unrelated” pathways can be simultaneously inhibited, suggesting a complete reversal to MDR.

肿瘤是人类生命的最大威胁之一。化疗是临床上治疗肿瘤的重要手段，然而肿瘤的多药耐药性严重制约了化疗效果。目前研究表明，引起肿瘤多药耐药性的主要原因可以分为“外排相关”和“外排无关”的机制。“外排相关”的耐药机制主要是由于细胞膜上ABC转运蛋白的过度表达进而将药物大量排出细胞，降低细胞内的药物积累量所引起的。而“外排无关”的耐药机制是由线粒体代谢途径相关的细胞内抗凋亡机制的激活引起的。本研究拟发展一种全新线粒体-siRNA复合体系以同步递送健康线粒体和功能siRNA至耐药肿瘤细胞中，通过siRNA的作用抑制药物外排，同时发挥健康线粒体的作用，改善细胞内的代谢环境，促进凋亡信号的激活与传递。该体系有望同时克服“外排相关”和“外排无关”的耐药机制，全面克服多药耐药性。

肿瘤是人类生命的最大威胁之一。化疗是临床上治疗肿瘤的重要手段，然而肿瘤的多药耐药性严重制约了化疗效果。目前研究表明，引起肿瘤多药耐药性的主要原因可以分为“外排相关”和“外排无关”的机制。“外排相关”的耐药机制主要是由于细胞膜上ABC转运蛋白的过度表达进而将药物大量排出细胞，降低细胞内的药物积累量所引起的。而“外排无关”的耐药机制是由线粒体代谢途径相关的细胞内抗凋亡机制的激活引起的。本研究拟发展一种全新线粒体-siRNA复合体系以同步递送健康线粒体和功能siRNA至耐药肿瘤细胞中，通过siRNA的作用抑制药物外排，同时发挥健康线粒体的作用，改善细胞内的代谢环境，促进的凋亡信号的激活与传递。该体系有望同时克服“外排相关”和“外排无关”的耐药机制，全面克服多药耐药性。