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

Nanomedicine : Nanotechnology, Biology, and Medicine
Tan YangGuangya Xiang

Abstract

Resistance 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.

Citations

Sep 29, 2020·International Journal of Nanomedicine·Jianguo WangXiao Xu
Aug 31, 2019·Cancers·Saranya Chidambaranathan Reghupaty, Devanand Sarkar
Dec 12, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jun GuoChuanrui Xu
Feb 4, 2021·Acta Pharmaceutica Sinica. B·Hongxia DuanWei Huang
Aug 13, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Jian SunZhaowei Chen
Jan 25, 2022·Technology in Cancer Research & Treatment·Ru WangWanwan Yi

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