A pH-responsive zinc (II) metalated porphyrin for enhanced photodynamic/photothermal combined cancer therapy

The acidic tumor microenvironment is triggered by glycolysis in hypoxic condition, which can motivate the pH-responsive system to build certain triggers for efficiently tumor-targeted phototherapy. Additionally, the metalated porphyrin structures are widely studied in biomedical applications due to the favorable properties of high singlet oxygen quantum yield as well as strong fluorescence imaging ability. Herein, a pH-responsive zinc (II) metalated porphyrin (P-4) was designed and synthesized for amplifying cancer photodynamic/photothermal therapy with excellent fluorescence quantum yield (67.4%), superb singlet oxygen quantum yield (84.3%) and desired photothermal conversion efficiency (30.0%). In vitro, the self-assembled P-4 nanoparticles can specifically target to lysosome subcellular site and realize protonated process of dibutaneaminophenyl (DBAP) groups with high photo toxicity. Under single 660 nm laser illumination, the tumor can be ablated completely with no side effects in vivo. This work demonstrates that the pH-responsive P-4 nanoparticles provide a new avenue for highly efficient cancer combination therapy.