Biocompatible hydrogel eradicates pregnancy-associated genital warts.

Current treatments for pregnancy-associated genital warts (PGW) often fail to balance safety and efficacy, especially during gestation. In this study, we introduce GelPV-5-ALA-Matrine, a smart, photoresponsive hydrogel designed for localized photodynamic therapy (PDT) targeting HPV-infected tissues. Co-delivery of 5-ALA and matrine facilitates mitochondrial autophagy through reactive oxygen species (ROS) elevation and MAPK8 activation. Using Mendelian randomization, we identified mitochondrial DNA copy number as a risk factor for sexually transmitted infections, supporting mitochondrial pathways as viable therapeutic targets. The hydrogel demonstrated strong in vitro efficacy in HPV-positive HeLa cells and significantly reduced wart burden and viral load in vivo under near-infrared (NIR) light. Molecular docking and functional validation highlighted MAPK8's key role in mediating ROS-induced mitochondrial clearance and apoptosis. Importantly, no systemic toxicity or adverse biochemical responses were observed. This innovative hydrogel system provides a blueprint for next-generation, patient-safe therapies for PGW and may be adaptable to other HPV-related pathologies in reproductive health.