In Situ Catalytic Reaction for Solving the Aggregation of Hydrophobic Photosensitizers in Tumor

The aggregation of hydrophobic photosensitizers limits the therapeutic effect of photodynamic therapy (PDT). Improving the hydrophilicity of photosensitizers can reduce their aggregation for enhancing PDT. Herein, a nanosystem (TPFcNP) is developed by a hydrophobic photosensitizer 5,10,15,20-tetrakis­(4-methacryloyloxyphenyl)­porphyrin (TMPP) containing multiple carbon–carbon double bonds and a ferrocene-containing amphiphilic block copolymer (PEG-b-PMAEFc), which catalyzes hydrogen peroxide (H₂O₂) to produce hydroxyl radicals (^•OH) in a tumor microenvironment by the Fenton reaction. The ^•OH could catalyze the addition reaction between the carbon–carbon double bonds of TMPP and overexpressed water-soluble glutathione (GSH) in tumor cells, which greatly improves the hydrophilicity of photosensitizers and reduces their aggregation. Experiments in vitro and in vivo have proved that this strategy significantly enhances the therapeutic efficacy of PDT. Catalyzing intracellular reactions in situ by making use of the tumor microenvironment will open up a new opportunity to solve the aggregation of materials in the tumor for cancer treatment.