Photothermal therapeutic effects and biosafety of a carbon nanoparticles–Fe(<scp>ii</scp>) complex for triple-negative breast cancer

Triple-negative breast cancer (TNBC) has become a major challenge in clinical treatment due to its highly aggressive nature and limited therapeutic options. A carbon nanoparticles-Fe(ii) complex (CNSI-Fe), as both a ferroptosis inducer and photothermal agent (PTA), could exert anticancer effects through the ferroptosis pathway and photothermal action. Herein, we evaluated the photothermal therapeutic effects of CNSI-Fe in mice bearing the model tumor of TNBC (4T1 tumor). The therapeutic effects of CNSI-Fe were compared without/with near-infrared (NIR) irradiation both <i>in vitro</i> and <i>in vivo</i>. The therapeutic mechanisms and biosafety were also investigated. CNSI-Fe exhibits excellent photothermal conversion efficiency. CNSI-Fe had significant cytotoxicity against TNBC cells, and photothermal therapy (PTT) further enhanced its antitumor effects. The combination of CNSI-Fe and PTT treatments exhibited a more pronounced tumor-suppressive effect and longer survival time comparing to single modality treatment. Mechanistic studies indicated that PTT facilitated the entry of iron ions from CNSI-Fe into cancer cells, generating more hydroxyl radicals and significantly enhancing the ferroptosis. The haematological and serum biological parameters associated with the histopathological observations indicated that the side-effects of CNSI-Fe were low during PTT. Overall, we evidenced the synergistic effect of CNSI-Fe chemotherapy and PTT for TNBC treatment with low toxicity.