Exploiting aza-zinc-dipyrromethene dyes for photoacoustic imaging guided synergistic anticancer phototherapy

Developing an innovative phototherapy agent that integrates tumor diagnosis and treatment functions is crucial for improving the precision and efficacy of anti-tumor treatment. Traditional aza-dipyrromethene (aza-DP) dyes exhibited strong photothermal effects, high molar absorption coefficients, and good photostability, but their photodynamic effects were weak. Metal elements were introduced into the aza-DP structure to address this issue, thereby enhancing inter-system crossing (ISC) and improving the photodynamic effect. In this study, a series of Zn(II)-chelated aza-DP complexes were designed and synthesized as novel phototherapy agents. To further extend the absorption wavelength of aza-DP in the near-infrared region, strong electron-donating groups of N,N-dimethylaniline were introduced at the 1,7 positions for modification, and both photodynamic and photothermal effects were also improved. The nanoparticles prepared by coating the phototherapy agents as mentioned above with amphiphilic DSPE-mPEG 5000 exhibit excellent hydrophilicity and photostability. Under 660 nm laser irradiation, the nanoparticles exhibited good synergistic therapeutic effects in vivo , with significant anti-tumor effects and minimal accompanying side effects. Meanwhile, considering its excellent photothermal properties, photoacoustic imaging technology was utilized to provide comprehensive guidance for the precise localization of tumors in mice. The study shows that rational modification of traditional aza-DP-based synergistic phototherapy agents can yield unexpected enhancements in their therapeutic effects, providing new ideas for anti-tumor drug development.