Improved tumor accumulation and photodynamic antitumor efficacy of a PEGylated photosensitizer.

Photodynamic therapy (PDT) has emerged as a promising modality for cancer treatment; however, the clinical translation of many photosensitizers remains limited by poor aqueous solubility, unfavorable biodistribution, and insufficient tumor accumulation. In this study, we investigated whether PEGylation of the photosensitizer Photomed could improve its physicochemical properties and in vivo photodynamic therapeutic efficacy without compromising its intrinsic photochemical activity. A PEG-conjugated Photomed (Photomed-PEG) was synthesized and systematically evaluated using singlet oxygen generation assays, cellular uptake studies, and in vitro phototoxicity assessments. In vivo biodistribution and antitumor efficacy were further examined in an A549 tumor-bearing mouse model. PEGylation markedly enhanced the aqueous solubility of Photomed while preserving efficient singlet oxygen generation and minimal dark toxicity. Moreover, Photomed-PEG exhibited enhanced tumor accumulation with reduced off-target retention compared to its non-PEGylated counterpart. These favorable pharmacokinetic properties translated into significantly improved photodynamic antitumor efficacy, as evidenced by pronounced tumor growth suppression following PDT. Importantly, no significant body weight loss or histopathological abnormalities in major organs were observed, indicating an acceptable safety profile. Collectively, these findings demonstrate that PEGylation represents an effective strategy for optimizing photosensitizer delivery and enhancing in vivo therapeutic performance for solid tumors.