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.