Manipulating the Aggregation of Phenoxazine-Modified Helical Boron-Dipyrromethene to Enhance Singlet Oxygen Generation for Efficient Tumor Therapy

A photosensitizer that exhibits high singlet oxygen (1O2) generation efficiency under moderate aggregation holds promise for combined photodynamic therapy (PDT) and chemotherapy. Here, we develop a phenoxazine-modified helical boron-dipyrromethene (PH-BODIPY) and manipulate its aggregation state to enhance the 1O2 generation efficiency. It demonstrates that under the moderately aggregated state, PH-BODIPY affords the highest 1O2 generation capability with a quantum yield of 53%. This is due to the inhibition of nonradiative transition and the reduction of the energy gap between the lowest singlet state and the triplet excited state. This unique property enables PH-BODIPY to persist with excellent 1O2 production capability when assembled with a chemotherapeutic drug, such as tamoxifen (TAM). By finely regulating the molar ratio of TAM and PH-BODIPY to 3:7 to optimize molecular aggregation, the resulting nanoparticles (NPs) achieve a 1O2 quantum yield of 55%. Subsequently, these NPs are successfully applied in the combined PDT and chemotherapy of tumor mice. This study highlights the design and aggregation-state regulation of a photosensitizer for enhanced photodynamic activity, paving the way for the development of combined chemotherapy strategies.