A crosslinked polyacrylamide hydrogel incorporating heptamethine cyanine enables synergistic photodynamic and photothermal ablation of melanoma cells

The low stability of photosensitizers (PSs) under physiological conditions limits the efficacy of photothermal (PTT) and photodynamic (PDT) therapy.To increase the efficacy of phototherapy, PSs can be integrated into hydrogels. However, hydrogels obtained by physical loading of PSs often suffer from early leakage, which diminishes therapeutic outcome.To address this problem, covalent attachment of PSs to the hydrogel network is proposed. In this study, a polyacrylamide hydrogelincorporating a heptamethinecyanine, which served asboth PS and covalent crosslinker, was designed and comprehensively characterized. Under NIR excitation, the hydrogel exhibited both photothermal and photodynamic features due to the presence ofheptamethine cyanine. The porous morphology was suitable for drug carriage, and light-triggered release of methotrexate (MTX)as a model drug was demonstrated. The hydrogel system was biocompatible with L929 cells in the dark, while a pronounced response was observed with human melanoma(SK MEL 30) cell line under illumination. Overall, the findings indicate that hydrogel is a viable platform for phototherapy and is well suited for controlled drug-delivery applications. A cyanine-based photosensitizer is integrated into a hydrogel as a crosslinker, preserving its photoactivity and enabling in vitro dual phototherapy for skin cancer.