Hydrogenated black TiO2-x-based core-shell nanocarriers cloaked with erythrocyte membranes for thermal imaging-monitored chemo-photothermal therapy.

Triple-negative breast cancer (TNBC) remains a major therapeutic challenge because of the lack of effective molecular targets, the limited efficacy of monotherapies, and the severe off-target toxicity associated with conventional chemotherapy. To address these limitations, we developed a biomimetic core-shell nanoplatform, denoted bT@M/D@P@R-DPF, for targeted chemo-photothermal therapy of TNBC. In this nanosystem, hydrogenated black TiO2-x (bT) provides NIR photothermal conversion and thermal imaging capability; the disulfide-bridged mesoporous organosilica shell enables redox-responsive DOX release; PDA functions as a pH-sensitive gatekeeper and auxiliary photothermal component; and the DSPE-PEG-FA-engineered erythrocyte membrane (R-DPF) coating contributes to biomimetic shielding and folate receptor-mediated tumor targeting. The resulting nanoparticles (NPs) exhibited good colloidal stability, efficient photothermal conversion, pH/GSH-responsive drug release, and minimal premature leakage. In 4T1 cells, folate-functionalized NPs achieved markedly enhanced cellular uptake and cytotoxicity under combined chemo-photothermal treatment compared with non-targeted NPs. In 4T1 tumor-bearing mice, bT@M/D@P@R-DPF significantly increased tumor accumulation and vascular permeability, yielding a tumor inhibition rate of 91% under 808 nm laser irradiation without detectable acute systemic toxicity. In addition, the thermal imaging capability enabled real-time monitoring of tumor localization and therapeutic response. Overall, this study presents an integrated biomimetic chemo-photothermal nanoplatform that may provide a feasible and effective strategy for the multimodal treatment of TNBC.