Combination therapy using microwave ablation and d-mannose-chelated iron oxide nanoparticles inhibits hepatocellular carcinoma progression  

作　　者：Rui Cui Luo Wang Dongyun Zhang Kun Zhang Jianping Dou Linan Dong Yixuan Zhang Jiapeng Wu Longfei Tan Jie Yu Ping Liang 

机构地区：[1]Department of Interventional Ultrasound,PLA General Hospital,Beijing 100853,China [2]Department of Medical Ultrasonics,the Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou 510655,China [3]Laboratory of Controllable Preparation and App Department of Medical Ultrasound,Shanghai Tenth People's Hospital,Tongji University School of Medicine,Shanghai 200072,China [4]Ultrasound Research and Education Institute,Tongji University School of Medicine,Shanghai 200072,China [5]Laboratory of Controllable Preparation and Application of Nanomaterials,Key Laboratory of Cryogenics,Technical Institute of Physics and Chemistry,Chinese Academy of Sciences,Beijing 100190,China

出　　处：《Acta Pharmaceutica Sinica B》2022年第9期3475-3485,共11页药学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China (Grant Nos. 91859201, 92159305, 81971625, and 82030047)

摘　　要：Despite being a common therapy for hepatocellular carcinoma(HCC),insufficient thermal ablation can leave behind tumor residues that can cause recurrence.This is believed to augment M2 inflammatory macrophages that usually play a pro-tumorigenic role.To address this problem,we designed D-mannose-chelated iron oxide nanoparticles(man-IONPs) to polarize M2-like macrophages into the antitumor Ml phenotype.In vitro and in vivo experiments demonstrated that man-IONPs specifically targeted M2-like macrophages and accumulated in peri-ablation zones after macrophage infiltration was augmented under insufficient microwave ablation(MWA).The nanoparticles simultaneously induced polarization of pro-tumorigenic M2 macrophages into antitumor M1 phenotypes,enabling the transformation of the immunosuppressive microenvironment into an immunoactivating one.Post-MWA macrophage polarization exerted robust inhibitory effects on HCC progression in a well-established orthotopic liver cancer mouse model.Thus,combining thermal ablation with man-IONPs can salvage residual tumors after insufficient MWA.These results have strong potential for clinical translation.

关 键 词：Microwave ablation Hepatocellular carcinoma Iron oxide nanoparticle Macrophage polarization Targeted therapy 

分 类 号：R735.7[医药卫生—肿瘤]