Biodegradable Polymeric Nanoparticle Employing a Photodynamic/Photothermal/Thermodynamic Combination Strategy for Treatment of Acute Maxillofacial Wound Infections

Abstract Wound infections remain difficult to treat with single‐mode photothermal (PTT), photodynamic (PDT), or thermodynamic therapy (TDT). To overcome these limitations, RDL3 nanoparticles are developed through co‐assembly of two functional polymers—LGMJ (PDT/PTT) and RMJ (TDT)—with DSPE‐mPEG 2000 . Under single‐wavelength NIR‐I irradiation, RDL3 simultaneously generates reactive oxygen species ( 1 O 2 and •OH) via LGMJ‐mediated PDT, produces mild hyperthermia (≤48 °C) through LGMJ's photothermal conversion, and releases carbon radicals (•C) from RMJ's heat‐cleavable azo bonds. This triple‐therapy synergy achieves >94% inhibition against multidrug‐resistant Staphylococcus aureus and Pseudomonas aeruginosa in vitro. In infected maxillofacial wounds in mice, RDL3+NIR‐I promotes near‐complete tissue restoration by eliminating pathogens through combined ROS/heat/radical action and activating endogenous tissue repair mechanisms. Crucially, self‐regulated biodegradation occurs via ROS‐sensitive thioketal bonds in LGMJ and heat‐labile azo bonds in RMJ, ensuring rapid clearance and high biosafety. RDL3 thus represents a biocompatible, broad‐spectrum platform for non‐antibiotic anti‐infective therapy.