Water-soluble hyperbranched polyglycerol photosensitizer for enhanced photodynamic therapy

Porphyrin and its derivatives as promising photosensitizers have been widely utilized in photodynamic therapy (PDT). However, the water-solubility and biocompatibility of porphyrins are the typical bottlenecks in clinical PDT processes. Herein, we successfully fabricated a new type of water-soluble, hyperbranched polyglycerol photosensitizer through one-step esterification between water-soluble hyperbranched polyglycerol (hbPG) and fluorophenylporphyrin (FP). Compared with the linear control polymer,i.e., FP covalently connected with linear polyethylene glycol (LPEG), the hyperbranched structures bearing multiple porphyrin units generated more singlet oxygen and exhibited higher cytotoxicity under laser irradiation. As an additional benefit of the hyperbranched structure, the aggregation of porphyrins could be significantly reduced, and greatly enhanced the drug-loading ratio of the single polymers. Base on a series ofin vitroandin vivoexperiments, we found that hbPG was capable of improving the water-solubility of porphyrin and enhancing the PDT effect. These results demonstrate that hbPG will have the opportunity to become an ideal substitute for traditional linear polymers in PDT.