Photothermal-immunotherapy of colon carcinoma by carbon nanoparticle-Fe(II) complex with immunoadjuvant

Ferroptosis is a regulated necrotic cell death pathway, which demonstrates significant anticancer potential. As the only ferroptosis-based nanomedicine under clinical trial evaluation, carbon nanoparticle-Fe (II) complex (CNSI-Fe) not only induces ferroptosis in tumor cells, but also serves as photothermal conversion agents for tumor photothermal therapy. In this study, we combined the treatments of CNSI-Fe, NIR irradiation and immunoadjuvant glycated chitosan (GC) to extend the use of CNSI-Fe from partial treatment to systemic therapy by arousing cancer immune response. In the established bilateral CT26.WT mouse models, CNSI-Fe + NIR (52 °C) + GC treatments triggered abscopal effects to induce systemic tumor regression. The inhibition rate was 96.10% for the primary tumor and 44.28% for the distant tumor. The supplement of GC largely enhanced the abscopal effects of CNSI-Fe photothermal therapy, where only the CNSI-Fe + NIR(52 °C) showed the inhibition rate of 16.68% for the distant tumor without GC. In addition to the ferroptosis induced by CNSI-Fe in the primary tumor, CNSI-Fe induced the release of tissue factors from primary tumors under NIR irradiation. GC captured these autologous cancer vaccines to initiate a systemic immune response. The long-term immune memory after the combination treatments was evidenced by the suppression of rechallenged tumors. The combination treatments showed acceptable toxicity during in vivo evaluations. Our study offered a translatable strategy for next-generation ISV and would hopefully benefit the patients in near future.