Diphenylamine modified phthalocyanine for phototherapy of melanoma

Phthalocyanines (Pc) have been widely employed as photosensitizers, but their rational design for application in the phototheranostics field remains challenging. Herein, a series of Pc derivatives with tunable electron-donating capabilities were designed to strengthen the intramolecular charge transfer (ICT) process. Upon the introduction of strong electron-donating substituents linked via nitrogen bridges, these complexes exhibited gradually red-shifted absorption maxima (up to 744 nm for PcMD), narrowed HOMO-LUMO gaps, quenched fluorescence emission, and promoted intersystem crossing (ISC). These favorable features consequently contributed to enhanced reactive oxygen species (ROS) generation and improved photothermal conversion efficiency. Further in vitro experiments were conducted using bovine serum albumin and folic acid co-modified PcMD (PcMD@BSA-FA). This nanoparticle exhibited strong photocytotoxicity to A375 melanoma cells upon 730 nm laser irradiation, and the corresponding half-maximal inhibitory concentration (IC₅₀) was determined to be 3.2 µM. In addition, this nanoparticle enabled concentration-dependent photoacoustic (PA) imaging, with prominent tumor accumulation reaching a maximum at 8 h post-injection. This work demonstrates that regulating the ICT process serves as an effective strategy to enhance the phototheranostic performance of Pc, and the PcMD@BSA-FA nanoparticles hold great potential for PA imaging-guided synergistic cancer phototherapy.