Triple-function porphyrin in glycopolymeric photosensitizers: from photoATRP to targeted PDT

Abstract

Porphyrin derivatives serve as photocatalysts in reversible-deactivation radical polymerization and as photosensitizers in photodynamic therapy (PDT). Herein, a triple function porphyrin, ZnTPPC6Br, was synthesized as a photocatalyst and initiator for photoATRP. Oxygen-tolerant photoATRP produced fructose-based star-shaped glycopolymers as targeted photosensitizers for PDT. ZnTPPC6Br/Cu^II/PMDETA could synthesize polymer photosensitizers with predictable M_n and low Đ. Mechanistic studies unveiled the transition of ZnTPPC6Br from a singlet excited state (¹PC*) to a triplet excited state (³PC*), enabling the activator Cu^I/L generation and initiating photoATRP. The excess ligands facilitate return of the active species to the ground state, while the presence of DMSO assists in oxygen depletion. Three fructose-based monomers with different polymerizable groups (acrylated, methacrylated, and p-vinylbenzoated) were employed to scale up polymerization, yielding glycopolymeric photosensitizers post-deprotection. In vitro cellular studies showed enhanced PDT efficacy of glycopolymeric photosensitizers against MCF-7 cells, attributed to specific GLUT5 binding for targeted endocytosis, highlighting their potential for precise cancer treatment compared to L929 cells. The multifunctional capabilities of ZnTPPC6Br are anticipated to serve as a strategic avenue for the advancement of polymer photosensitizers with potential PDT applications.