Enhanced Photosensitizer-Embedded Glycopolymers through Self-Catalytic PET-RAFT Polymerization for Targeted PDT

PET-RAFT polymerization enables precise polymer synthesis, yet conventional systems require an excess chain transfer agent (CTA) over unbound photocatalysts (PCs). Herein, a self-catalyzed strategy employing polymerizable porphyrin MTPPZnH as a dual-functional PC effectively embeds high photosensitizer content into glycopolymers for photodynamic therapy (PDT). Three galactose-bearing monomers (acrylate, methacrylate, 4-vinylbenzoate) were polymerized via PET-RAFT under optimized light conditions, achieving satisfactory M and relatively narrow Đ. Mechanistic studies revealed that photoexcited MTPPZnH transfers electrons/energy to CTA via a PET process, initiating polymerization, with DMSO enhancing oxygen depletion. Water-soluble glycopolymeric photosensitizers exhibited high fluorescence and singlet oxygen quantum yield. In vitro, galactose-bearing photosensitizers showed superior ASGPR-mediated endocytosis in HepG2 cells over Huh-7 and MCF-7 cells, enabling targeted PDT. The incorporation of MTPPZnH contributes to an effective multifunctional strategy, offering a promising approach for the development of high photosensitizer-embedded polymeric photosensitizers for potential PDT applications.