Acta Pharmaceutica Sinica B (Sep 2022)

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

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

DOI
https://doi.org/10.1016/j.apsb.2022.05.026
Journal volume & issue
Vol. 12, no. 9
pp. 3475 – 3485

Abstract

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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.

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