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

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.

• Authors: 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 Xiang
• Journal: Nanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 14 Issue 7 Pg. 2009-2021 (10 2018) ISSN: 1549-9642 [Electronic] United States
• PMID: 29842934 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• BMI1 protein, human
• Cations
• Nanocapsules
• RNA, Small Interfering
• Polycomb Repressive Complex 1
• Cisplatin

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacology)
• Apoptosis
• Carcinoma, Hepatocellular (genetics, pathology, therapy)
• Cations
• Cell Cycle
• Cell Proliferation
• Cisplatin (administration & dosage, pharmacology)
• Combined Modality Therapy
• Drug Resistance, Neoplasm
• Humans
• Liver Neoplasms (genetics, pathology, therapy)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Nanocapsules (administration & dosage, chemistry)
• Neoplastic Stem Cells (drug effects, metabolism, pathology)
• Polycomb Repressive Complex 1 (antagonists & inhibitors, genetics)
• RNA, Small Interfering (genetics)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays