Combination therapy using microwave ablation and d-mannose-chelated iron oxide nanoparticles inhibits hepatocellular carcinoma progression.
10.1016/j.apsb.2022.05.026
- Author:
Rui CUI
1
;
Luo WANG
1
;
Dongyun ZHANG
1
;
Kun ZHANG
2
;
Jianping DOU
1
;
Linan DONG
1
;
Yixuan ZHANG
1
;
Jiapeng WU
1
;
Longfei TAN
3
;
Jie YU
1
;
Ping LIANG
1
Author Information
1. Department of Interventional Ultrasound, PLA General Hospital, Beijing 100853, China.
2. Laboratory of Controllable Preparation and App Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
3. 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.
- Publication Type:Journal Article
- Keywords:
Hepatocellular carcinoma;
Iron oxide nanoparticle;
Macrophage polarization;
Microwave ablation;
Targeted therapy
- From:
Acta Pharmaceutica Sinica B
2022;12(9):3475-3485
- CountryChina
- Language:English
-
Abstract:
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 M1 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.
