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 usu...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.展开更多
基金supported by the National Natural Science Foundation of China (Grant Nos. 91859201, 92159305, 81971625, and 82030047)
文摘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.
