Ferritin-Doped Nanoparticles Triggered Tumor-Specific Darkening for Enhanced Photothermal Tumor Ablation and Immune Activation.

Combining the lysosomal targeting ability of human ferritin heavy chain (HFn) and the strong oxidizing property of gallic acid-iron complex (GA-Fe), a hybrid nanoparticle HFn/GA-Fe was synthesized by a cross-linking reaction. We discovered that HFn/GA-Fe would specifically darken the color of tumors after intravenous injection without rendering notable toxicity in normal organs, as observed by visual inspection and photoacoustic imaging. HFn/GA-Fe specifically bound to HFn receptor (TfR1/TIM-2) and aggregated at the lysosomal pH. HFn/GA-Fe induced endothelial cell death and tumor-specific hemorrhage by generating reactive oxygen species (ROS). Under laser irradiation, the leaked deoxyhemoglobin significantly enhanced the photothermal effect and subsequently triggered anti-tumor immune responses. The cavities of ferritin nanocages can further encapsulate drugs, endowing them with broader application prospects.