Water-soluble benzylidene cyclopentanone photosensitizers for two-photon excited photodynamic therapy

A series of benzylidene cyclopentanone photosensitizers modified by polyethylene glycol, carboxylate anionic or pyridyl cationic groups with gradient lipid-water partition coefficients were reported. Detailed characterization and systematic studies of these photosensitizers, including their linear and nonlinear photophysical properties, in vitro photodynamic therapy (PDT) and two-photon excited PDT (2PE–PDT) activities were conducted and compared with a clinical drug PSD-007 (a mixture of porphyrins). Three of them exhibited appropriate lipid-water partition coefficients, high reactive oxygen yields, large two-photon absorption cross-section and low dark toxicity under therapy dosage, could be absorbed efficiently by liver hepatocellular HepG2 cells and presented strong PDT and 2PE-PDT activity by in vitro cell experiments. Furthermore, in vivo tumor experiments were carried out on BALB/c mouse models using B3 as the photosensitizer. The results showed that the tumor growth could be effectively suppressed by B3 under 2PE-PDT. This work demonstrated the feasibility of using a simple molecular structure to construct high efficient photosensitizers for 2PE-PDT.