Aggregation control of phthalocyanines via Tween 20 micelles for improved photodynamic cytotoxicity

Photodynamic therapy (PDT) is a promising modality for selective cancer treatment; however, aggregation of hydrophobic photosensitizers in aqueous environments often leads to fluorescence quenching, reduced reactive oxygen species (ROS) generation, and diminished photocytotoxicity. In this study, we designed a micellar delivery system based on Tween 20, a biocompatible nonionic surfactant composed of a polyoxyethylene hydrophilic chain and a sorbitan ester–derived hydrophobic moiety, to optimize the photochemical performance of phthalocyanine photosensitizers. The micellar hydrophobic core was intended to encapsulate the photosensitizer through hydrophobic interactions and π–π stacking, thereby suppressing aggregation, while the hydrated polyoxyethylene shell provided steric stabilization and minimized nonspecific biological interactions. This core–shell architecture was designed to maintain the photosensitizer in a monomeric or weakly associated state, enabling efficient photoactivation and singlet oxygen generation. Photocytotoxicity toward HeLa cells was evaluated using the MTT assay. Micellized ZnPc-OH exhibited significantly enhanced light-induced cytotoxicity at 0.08 and 0.16 mg mL −1 compared with non-irradiated controls, whereas micellized ZnBuPc-OH showed only concentration-dependent cytotoxicity without a clear light-dependent effect. These findings indicate that the optimized Tween 20 micellar environment facilitates efficient ROS generation, suitable micellar encapsulation, and favorable cellular uptake/localization for ZnPc-OH, thereby preserving photocytotoxic activity. Overall, this study demonstrates that rational micellar design can mitigate aggregation-induced deactivation of hydrophobic photosensitizers and represents a viable strategy for improving PDT efficacy.