Improved Photocytotoxicity Based on Triblock Polymer-Derived Nanostructure

Enhancing singlet oxygen generation for photosensitizers in aqueous media can markedly improve the efficacy of photochemical therapy. Herein, triblock polymers composed of pyropheophorbide a photosensitizer (PPa), polyethylene glycol, and phospholipid are synthesized. These triblock polymers, driven by hydrophilic-hydrophobic interactions, spontaneously fold into an amphiphilic structure and further self-assemble into nanomicelles. This novel nanomicelle, termed nanoPPa, provides a stable, nonpolar microenvironment for photosensitizer molecules, thereby enhancing photodynamic energy efficiency by minimizing energy loss from molecular collisions and self-aggregation. Compared to the photosensitizer PPa alone, nanoPPa exhibits a remarkable fivefold increase in singlet oxygen generation, accompanied by a substantial boost in phototoxicity. Simultaneously, an increased fluorescence emission is observed. These enhancements in phototoxicity and fluorescence signify the potential of nanoPPa for dual applications in photodynamic therapy (PDT) and photodynamic imaging (PDI). The fabrication of this nanostructure is proposed as a versatile strategy to improve the application of photosensitizers and enhance therapeutic outcomes.