Design the synthesis of AIEgen photosensitizers for regulating the level of PTX in drug-resistant tumor cells

The general mechanism of chemotherapeutic resistance is related to changes in the uptake and efflux rate of chemotherapeutic drugs or intracellular transport. In the progress of photodynamic and PTX combination therapy, the excessive use of photosensitizers (PSs) may cause side effects. Since PSs are exposed to light, they can still cause ongoing damage to normal cells. To effectively reduce this side effect, we propose a strategy to regulate the concentration of PTX in resistant cells using low concentrations of AIEgen PSs. In this work, the molecular structure of four AIEgen PSs (TPEPy, TPECPy, TPAPy, and TPESPy) were designed and synthesized featuring different “D−π−A” type structures. They displayed excellent optical properties, good biocompatibility, good PDT effect, mitochondrial targeting and cell imaging. Among these AIEgen PSs, TPESPy exhibited the strongest PDT effect in tumor cells and PTX resistant tumor cells. The reversal coefficient of PTX resistant tumor cells can be achieved as 2214. In addition, to demonstrate the transport mechanism of PTX within tumor cells, we further study the effect of uptake and expel PTX in the PTX resistant SKOV-3 cells. The results show the rate of uptake and expel PTX for PTX resistant SKOV-3 cells can be effectively changed by controlling the concentration of AIEgen PSs and light irradiation time, providing precise treatment options for drug-resistant tumor cells.