Hypotoxic amphiphilic polymers with high fluoride content as oxygen carriers enhance photodynamic therapy against hypoxic tumors

Abstract

Photodynamic therapy (PDT) eradicates cancer cells by transforming tumor oxygen into highly reactive singlet oxygen (¹O₂) through a photosensitizer. However, pre-existing hypoxia within tumors and oxygen consumption during PDT can cause insufficient oxygen supply, hence hindering the effectiveness of this treatment modality. Fluorides, renowned for their excellent biocompatibility and oxygen affinity, have been widely applied in medical environments as carriers. In this study, a hypotoxic amphiphilic fluorinated polymer (PEGAF) was synthesized using polyethylene glycol methyl ether acrylate (PEGA) and perfluorooctyl acrylate (PFOEA) as monomers through the atomic transfer radical polymerization (ATRP) technology and used as carriers for oxygen and the photosensitizer chlorin e6 (Ce6). Experimental results demonstrated that PEGAF@Ce6-O₂ substantially improved the hypoxic microenvironment of tumors and significantly inhibited tumor growth, markedly enhancing the outcome compared to sole PDT application. This study proposes a new strategy for enhancing the efficacy of PDT.