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 in-flammatory 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 M1 phenotype.In vitro and in vivo experiments demonstrated that man-IONPs specifically tar-geted M2-like macrophages and accumulated in peri-ablation zones after macrophage infiltration was augmented under insufficient microwave ablation(MWA).The nanoparticles simultaneously induced po-larization of pro-tumorigenic M2 macrophages into antitumor Ml phenotypes,enabling the transforma-tion 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 af-ter insufficient MWA.These results have strong potential for clinical translation.

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

Department of Interventional Ultrasound,PLA General Hospital,Beijing 100853,China;Department of Medical Ultrasonics,the Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou 510655,China;Laboratory of Controllable Preparation and App Department of Medical Ultrasound,Shanghai Tenth People's Hospital,Tongji University School of Medicine,Shanghai 200072,China;Ultrasound Research and Education Institute,Tongji University School of Medicine,Shanghai 200072,China;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

药学学报（英文版）

[1]Rui Cui;Luo Wang;Dongyun Zhang;Kun Zhang;Jianping Dou;Linan Dong;Yixuan Zhang;Jiapeng Wu;Longfei Tan;Jie Yu;Ping Liang-.Combination therapy using microwave ablation and D-mannose-chelated iron oxide nanoparticles inhibits hepatocellular carcinoma progression)[J].药学学报（英文版）,2022(09):3475-3485

immunoactivating

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