He Xiaojun, Wang Zijian, Mao Bangxun, Lin Hao, Jin Xuru, Du Mengxuan, Huang Binge, Xin Songlin, Qu Jinmiao, Feng Yun
Department of Ophthalmology, Peking University First Hospital, Beijing, 100034, China.
School of Ophthalmology & Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Bioact Mater. 2025 Jun 27;51:841-857. doi: 10.1016/j.bioactmat.2025.06.043. eCollection 2025 Sep.
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 wound healing while reducing inflammatory cytokine levels, alongside exhibiting excellent biocompatibility. This study transcends the limitations of traditional single-modal therapies by achieving precise synergy between nanozyme catalytic activity and physical field responses, establishing a novel "diagnosis-treatment-regulation" integrated paradigm for managing deep-seated tissue infections. Through engineered design and surface topological optimization, we successfully resolve the critical balance between nanozyme catalytic efficiency and biosafety, thereby laying the theoretical foundations for developing intelligent anti-infective materials.
为应对深部组织耐药细菌感染带来的治疗挑战,本研究创新性地开发了一种基于铂钯金三金属合金纳米酶(PPA)的多模态协同治疗平台。通过克服传统光动力疗法(PDT)和电动力疗法的局限性,如组织穿透受限和操作复杂等问题,本研究整合了三种优势策略:光热疗法(PTT)、化学动力疗法(CDT)和声动力疗法(SDT),构建了具有分级纳米结构的PPA系统。该纳米平台凭借其独特的多分支结构实现了对细菌生物膜屏障的有效穿透,同时展现出超声(US)-激光双激活级联催化效应和多模态协同杀菌机制。结果表明,在近红外激光和US联合刺激下,PPA产生显著的温度梯度(光热转换效率为52.21%)并爆发活性氧(ROS),有效破坏生物膜基质并根除细菌(抑制率为95%)。综合转录组学和蛋白质组学分析表明,PPA通过多种机制发挥作用,包括调节氧化应激途径、群体感应系统和代谢网络。动物模型表明,PPA能够加速深部感染伤口愈合并降低炎症细胞因子水平,同时具有出色的生物相容性。本研究通过实现纳米酶催化活性与物理场响应之间的精确协同,超越了传统单模态疗法的局限性,建立了一种用于管理深部组织感染的新型“诊断-治疗-调控”一体化模式。通过工程设计和表面拓扑优化,我们成功解决了纳米酶催化效率与生物安全性之间的关键平衡问题,从而为开发智能抗感染材料奠定了理论基础。
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