肝细胞癌
医学
阿霉素
化疗
癌症研究
化学
不利影响
药物输送
转移
肿瘤科
内科学
药理学
癌症
有机化学
作者
Jinshun Xu,Xueqing Cheng,Longfei Tan,Changhui Fu,Muneeb Ahmed,Hui Hui,Jianping Dou,Qunfang Zhou,Xiangling Ren,Qiong Wu,Sanyi Tang,Hongqiao Zhou,Xianwei Meng,Jie Yu,Ping Liang
出处
期刊:Nano Letters
[American Chemical Society]
日期:2019-04-01
卷期号:19 (5): 2914-2927
被引量:67
标识
DOI:10.1021/acs.nanolett.8b05202
摘要
Hepatocellular carcinoma (HCC) with metastatic disease is associated with a low survival in clinical practice. Many curative options including liver resection, transplantation, and thermal ablation are effective in local but limited for patients with distant metastasis. In this study, the efficacy, specificity, and safety of P-selectin targeted delivery and microwave (MW) responsive drug release is investigated for development of HCC therapy. By encapsulating doxorubicin (DOX) and MW sensitizer (1-butyl-3-methylimidazolium-l-lactate, BML) into fucoidan conjugated liposomal nanoparticles (TBP@DOX), specific accumulation and prominent release of DOX in orthotopic HCC and lung metastasis are achieved with adjuvant MW exposure. This results in orthotopic HCC growth inhibition that is not only 1.95-fold higher than found for nontargeted BP@DOX and 1.6-fold higher than nonstimuli responsive TP@DOX but is also equivalent to treatment with free DOX at a 10-fold higher dose. Furthermore, the optimum anticancer efficacy against distant lung metastasis and effective prevention of widespread dissemination with a prolonged survival is described. In addition, no adverse metabolic events are identified using the TBP@DOX nanodelivery system despite these events being commonly observed with traditional DOX chemotherapy. Therefore, administering TBP@DOX with MW exposure could potentially enhance the therapeutic efficacy of thermal-chemotherapy of HCC, especially those in the advanced stages.
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