Trimetallic Pt-Pd-Au alloy nanozymes for multimodal synergistic therapy to overcome deep-seated drug-resistant infections via ROS cascade

作者：Xiaojun He, Zijian Wang, Bangxun Mao, Hao Lin, Xuru Jin, Mengxuan Du, Binge Huang, Songlin Xin, Jifeng Qu, Yun Feng · 发表于：Bioactive Materials · 年份：2025 · DOI：10.1016/j.bioactmat.2025.06.043 · 被引用次数：24 · 研究领域：Advanced Nanomaterials in Catalysis、Nanoplatforms for cancer theranostics、Advanced biosensing and bioanalysis techniques

To address the therapeutic challenges posed by deep-tissue drug-resistant bacterial infections, this study innovatively develops a multimodal synergistic therapeutic platform based on platinum-palladium-gold trimetallic alloy nanozymes (PPA). By overcoming the limitations of conventional photodynamic therapy (PDT) and electrodynamic therapy, such as restricted tissue penetration and operational complexity, this research integrates three advantageous strategies: photothermal therapy (PTT), chemodynamic therapy (CDT), and sonodynamic therapy (SDT) to construct a PPA system characterized by hierarchical nanostructures. The nanoplatform achieves efficient penetration through bacterial biofilm barriers attributed to its unique multi-branched architecture while exhibiting ultrasound (US)-laser dual-activated cascade catalytic effects and multimodal synergistic bactericidal mechanisms. Results demonstrate that PPA generates significant temperature gradients (with a photothermal conversion efficiency of 52.21 %) and bursts of reactive oxygen species (ROS) under combined near-infrared laser and US stimulation, effectively disrupting biofilm matrices and eradicating bacteria (with an inhibition ratio of 95 %). Integrated transcriptomic and proteomic analyses reveal that PPA operates through multiple mechanisms including the regulation of oxidative stress pathways, quorum sensing systems, and metabolic networks. Animal models illustrate the capability of PPA to accelerate deep infection...