Ding Li, Sun Ruonan, Zhang Xinyue
College of Bioscience and Biotechnology, Yangzhou University, Yangzhou, Jiangsu 225009, China.
Institute of Comparative Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China.
Oncotarget. 2017 Mar 28;8(13):21200-21211. doi: 10.18632/oncotarget.15508.
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.
Rap2b是我们最近鉴定出的一种新型p53靶点。敲低Rap2b可使HCT116细胞对阿霉素诱导的凋亡敏感，这表明Rap2b促进癌细胞对阿霉素的耐药性。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作为抗人类癌症治疗剂的潜力。具体而言，与HCT116细胞共孵育后，负载阿霉素和Rap2b siRNA的金纳米壳被内化。随后的激光照射促进了阿霉素和Rap2b siRNA从纳米颗粒中的释放。激光诱导的Rap2b siRNA释放降低了细胞中Rap2b的表达，并显著增强了阿霉素在体外和体内的抗癌治疗效果。此外，纳米颗粒的激光照射可能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。总之，Rap2b siRNA是基于阿霉素的抗癌治疗的潜在增强剂，同时携带阿霉素和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景的抗癌治疗策略。
