Novel nanoparticle CS-C60-Fe3O4 magnetically induces tissue-specific aggregation and enhances thermal ablation of hepatocellular carcinoma

Abstract Metallofullerenes are an important type of metallic nanomaterial with promising applications in several medical fields. Thermal ablation, including radiofrequency ablation (RFA) and microwave ablation (MWA), is an important treatment strategy for advanced hepatocellular carcinoma (HCC). The thermal expansion of fullerenes makes them good adjuncts to thermal ablation treatment of HCC. In this study, we used an innovative method of emulsification and cross-linking to produce CS-C60-Fe3O4 (Chitosan-C60-Fe3O4) nanoparticles, which have the advantages of uniform particle size and high bioavailability, as a kind of novel nano-pharmaceutical. The CS-C60-Fe3O4 nanoparticles were prepared by the cross-linking reaction from chitosan–acetic acid solution, Fe3O4 nanoparticles by Fe2SO4·7H2O and FeCl3·6H2O, and C60. The average particle size of CS-C60-Fe3O4 was 194.3 nm. Because CS-C60-Fe3O4 is magnetic, it can achieve specific and tissue aggregation in HCC tumor tissues. Moreover, compared with normal soluble C60 (EL35-C60), CS-C60-Fe3O4 prolonged the retention time of C60 in the blood of mice. CS-C60-Fe3O4 alone is not cytotoxic to cultured cells or tumor tissues, but when combined with thermal ablation strategies (RFA and MWA), it significantly upregulates the antitumor effects of thermal ablation on HCC tissues, that is, it acts as a sensitiser to thermal ablation. In the presence of thermal ablation, CS-C60-Fe3O4 interfered with iron metabolism in HCC cells and induced ferroptosis of HCC cells in the tumor tissues. These results not only expand our understanding of metallofullerenes but also provide additional options for the treatment of advanced HCC.