Enhancing the therapeutic effect via elimination of hepatocellular carcinoma stem cells using Bmi1 siRNA delivered by cationic cisplatin nanocapsules
Enhancing the therapeutic effect via elimination of hepatocellular carcinoma stem cells using Bmi1 siRNA delivered by cationic cisplatin nanocapsules
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阳离子顺铂纳米胶囊递送的 Bmi1 siRNA 通过消除肝细胞癌干细胞增强治疗效果
DOI：
10.1016/j.nano.2018.05.012
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Xiang Guangya
中科院分区：
文献类型：
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作者：
Yang Tan;Chen Yuyuan;Zhao Pengxuan;Xue Huiying;You Jia;Li Bin;Liu Yong;He Chuanchuan;Zhang Xiaojuan;Fan Lingling;Lee Robert J;Li Lei;Ma Xiang;Xu Chuanrui;Xiang Guangya
肝细胞癌（HCC）对全身化疗的耐药性部分是由于耐药癌症干细胞的存在。Bmi 1蛋白对肝癌干细胞（CSCs）的存活和增殖至关重要。在这里，我们报告了负载在顺铂（NPC）阳离子纳米胶囊中的Bmi 1 siRNA（Bmi 1 siR）消除小鼠原位HCC中的干细胞。NPC/Bmi 1 siR是通过静电复合Bmi 1 siRNA与以顺铂为核心、阳离子脂质体包裹的NPC的方法制备的，NPC/Bmi 1 siR在荷肝癌小鼠体内的抗肿瘤活性明显高于顺铂和NPC。重要的是，体外流式细胞术（FACS）分析和体内组织学检查均显示，NPC/Bmi 1 siR处理显著减少了侧群或CD 133 + HCC细胞，表明HCC CSC被消除。总之，我们的研究结果表明，肝癌的耐药性可以通过在阳离子纳米胶囊中共递送Bmi 1 siRNA与顺铂来克服。
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 cellsin situHCC in mice. NPC/Bmi1siR was fabricatedviaelectrostatic 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) analysisin vitroand histological examinationin vivorevealed 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.