Ultrasound-activated bimetallic PtRu alloy nanozymes for synergistic sonodynamic and chemodynamic therapy of multidrug-resistant bacterial infection.

Deep-seated infections caused by multidrug-resistant (MDR) bacteria, such as pneumonia and abscesses, present significant therapeutic challenges due to their complex pathological microenvironments, which often limit the efficacy of conventional antibiotic treatments. The increasing emergence of MDR bacteria, along with their ability to rapidly acquire resistance, has intensified the need for novel therapeutic strategies. The advancement of nanotechnology has facilitated the development of non-antibiotic-dependent treatment modalities, which are increasingly preferred due to their high efficiency, non-invasiveness, and resistance-free properties. In this study, guided by density functional theory (DFT) predictions, we designed an ultrasound (US)-activated bimetallic Pt(x)Ru(y) alloy nanozyme (PR) that synergistically combines US-activated sonodynamic therapy (SDT) with chemodynamic therapy (CDT) for precise control of reactive oxygen species (ROS) generation. By carefully optimizing the atomic ratio of platinum (Pt, catalytic sites) to ruthenium (Ru, adsorption sites), we synthesized ultrafine bimetallic alloy nanoplatforms with enhanced functional performance. Both theoretical simulations and experimental characterizations confirmed that PR exhibits exceptional oxidase-like and peroxidase-like activity, facilitating enhanced US-triggered ROS production through amplified sonodynamic effects. The PR demonstrated significant in vitro antibacterial activity, effectively disrupted biofilms, and showed excellent biocompatibility. In mouse models of pneumonia and subcutaneous abscesses, PR facilitated rapid bacterial clearance and modulation of the inflammatory microenvironment. This study presents a novel, non-antibiotic biocatalytic platform that provides a rational design strategy for bimetallic alloy nanozymes, offering a promising therapeutic approach for the synergistic treatment of MDR bacterial infections. These findings underscore the translational potential of multifunctional nanoplatforms in addressing the growing challenge of antibiotic resistance.