Localized gold nanoparticle-mediated radiosensitization without systemic exposure via polyurethane electrospun patches enabling site-specific gastric tumor therapy

Radiotherapy represents a critical challenge in the treatment of gastric tumors. Gold nanoparticles (AuNPs) are radiosensitizers able to locally increase the dose effect and the formation of reactive oxygen species (ROS) considering their high atomic number, possibility of surface functionalization and biocompatibility. However, the potential bioaccumulation associated with their administration and consequent systemic release gives rise to concerns regarding their clinical translation. In this study, an innovative approach is proposed for local provision of 100 nm AuNPs through their integration into thermoplastic polyurethane (TPU) electrospun fibers creating a radiosensitizing patch. The incorporation of AuNPs is tested under four distinct concentrations (2.5, 5, 15 and 25 µg/cm²), employing two distinct methodologies: blending and coating. Physicochemical and mechanical characterization of the developed patch show stability in gastric environments up to 28 days. In addition, evaluation of ROS generation shows the higher performance of the coating compared to the blending, for all concentrations tested. Biological evaluation demonstrates the effectiveness against AGS and MKN45 cell lines compared to non-tumoral NST20 cells. A decrease of more than 20% in the amount of viable DNA is observed in all cell lines on day 7 after exposure to radiation of both 6 MV with and without flattening filter.