Enhancing the therapeutic effect via elimination of hepatocellular carcinoma stem cells using Bmi1 siRNA delivered by cationic cisplatin nanocapsules

Publication date: Available online 26 May 2018Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Tan Yang, Yuyuan Chen, Pengxuan Zhao, Huiying Xue, Jia You, Bin Li, Yong Liu, Chuanchuan He, Xiaojuan Zhang, Lingling Fan, Robert J. Lee, Lei Li, Xiang Ma, Chuanrui Xu, Guangya XiangResistance of hepatocellular carcinoma (HCC) to systemic chemotherapy is partially due to presence of drug-resistant cancer stem cells. Bmi1 protein is essential for survival and proliferation of HCC cancer stem cells (CSCs). Here, we report that Bmi1 siRNA (Bmi1siR) loaded in cationic nanocapsules of cisplatin (NPC) eliminated stem cells in situ HCC in mice. NPC/Bmi1siR was fabricated via electrostatic complexation of Bmi1 siRNA to NPCs, which had cores composed of cisplatin and were coated with cationic lipids. In vivo, NPC/Bmi1siR showed higher anti-tumor activity in HCC bearing mice compared with cisplatin or NPC. Critically, both flow cytometry (FACS) analysis in vitro and histological examination in vivo revealed that side population or CD133+ HCC cells were dramatically decreased by NPC/Bmi1siR treatment, suggesting that HCC CSCs were eliminated. Altogether, our results suggest that drug resistance of HCC can be overcome by co-delivering Bmi1 siRNA with cisplatin in cationic nanocapsules.Graphical abstractAn illustration of intracellular trafficking of NPC/Bmi1siR nanocapsules. After injection, NPC/Bmi1siR nanocapsules escape from blood vessel and enter to the tumor. NPC/Bmi1si...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research