A pH-responsive N-heterocyclic carbene stabilized AuPdH nanoplatform for integrated photothermal and hydrogen-mediated biofilm eradication

Photothermal therapy is an effective approach to overcome bacterial antibiotic resistance; however, challenges remain in improving the targeting of photothermal agents and minimizing inflammation to healthy tissues. Herein, we present hydrogen-loaded AuPd nanoparticles stabilized through strong metal-carbene interactions using a micro-environment responsive N-heterocyclic carbene ligand (NHC-AuPdH), intended to effectively combat biofilm infections by photothermal effect. The NHC-AuPdH nanoparticles exhibit pH-responsiveness, whereby protonation of NHC induces a positive surface charge of nanoparticles in the acidic environment of biofilms. These positively charged nanoparticles enhance electrostatic interactions with the negatively charged bacterial surfaces, providing a versatile platform for targeted therapeutic applications. Meanwhile, the hydrogen stored in NHC-AuPdH nanoparticles is released by near infrared irradiation to react with reactive oxygen species and therewith eliminate inflammation induced by hyperthermia and bacterial infections. Furthermore, the NHC-AuPdH nanoparticles are accelerating wound healing by simultaneously facilitating rapid bacterial biofilm eradication and inflammation relief to protect healthy tissue and promote angiogenesis. This study provides a new micro-environment responsive N-heterocyclic carbene ligand as a general chemical platform for stabilizing metal nanoparticles and enabling targeted antibacterial therapy. A pH-responsive NHC-stabilized AuPdH nanoplatform was developed, integrating photothermal and hydrogen therapies for efficient eradication of bacterial biofilms while minimizing hyperthermia-induced damage to normal tissues. • Alloyed Au-Pd structure enhances photothermal conversion. • Positive charge of NHC ligands enhances nanoparticle penetration and electrostatic interaction with bacterial biofilms. • Released H 2 scavenges ROS and reduced hyperthermia-induced damage to healthy cells. • Combined photothermal and hydrogen therapy accelerate angiogenesis and improved wound healing.