Rap2b siRNA significantly enhances the anticancer therapeutic efficacy of adriamycin in a gold nanoshell-based drug/gene co-delivery system.
Rap2b siRNA significantly enhances the anticancer therapeutic efficacy of adriamycin in a gold nanoshell-based drug/gene co-delivery system.
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DOI：
10.18632/oncotarget.15508
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发表时间：
2017-03-28
期刊：
影响因子：
--
通讯作者：
Zhang X
中科院分区：
文献类型：
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作者：
Ding L;Sun R;Zhang X
Rap2b是我们最近发现的一个新的p53靶点。Rap2b的敲低使HCT 116细胞对阿霉素诱导的凋亡敏感，表明Rap2b促进癌细胞中的阿霉素抗性。在本研究中，我们设计了一种基于纳米结构的药物/基因递送系统，以评估Rap2b siRNA作为人类癌症治疗剂的潜力。具体地，在与HCT 116细胞共孵育后，阿霉素和Rap2b siRNA负载的金纳米壳被内化。随后的激光照射促进阿霉素和Rap2b siRNA从纳米颗粒中释放。激光诱导Rap2b siRNA的释放降低了Rap2b的细胞表达，并显著增强了阿霉素在体外和体内的抗癌治疗效果。此外，激光照射纳米粒子可能会对癌细胞产生额外的热杀伤作用，并进一步提高阿霉素的抗癌疗效。综上所述，Rap2b siRNA是一种潜在的增强剂，用于基于阿霉素的抗癌治疗，并且携带阿霉素和Rap2b siRNA的基于金纳米壳的药物/基因递送系统提供了一种有前途的抗癌治疗策略。
Rap2b is a novel p53 target we have identified recently. Knockdown of Rap2b sensitizes HCT116 cells to adriamycin-induced apoptosis, indicating that Rap2b promotes adriamycin resistance in cancer cells. In the present study, we designed a nanostructure-based drug/gene delivery system to evaluate the potential of Rap2b siRNA as a therapeutic agent against human cancers. Specifically, after co-incubated with HCT116 cells, adriamycin- and Rap2b siRNA-loaded gold nanoshells were internalized. Subsequent laser irradiation promoted release of adriamycin and Rap2b siRNA from the nanoparticles. The laser-induced release of Rap2b siRNA decreased cellular expression of Rap2b and significantly enhanced the anticancer therapeutic efficacy of adriamycin in vitro and in vivo. In addition, laser irradiation of the nanoparticles might exert an additional thermal killing effect on cancer cells and further improved the anticancer efficacy of adriamycin. In summary, Rap2b siRNA is a potential enhancing agent for adriamycin-based anticancer therapeutics and the gold nanoshell-based drug/gene delivery system carrying both adriamycin and Rap2b siRNA provides a promising anticancer therapeutic strategy.