Ytterbium-biomineralized nanoplatform-mediated mild photothermal therapy for implant-associated infections caused by multidrug-resistant Pseudomonas aeruginosa.
Abstract
Bacterial infection remains a major contributor to implant surgery failure and unfavorable patient outcomes. Unlike superficial wound infections, bacterial implant-related infections (IRIs) often develop in deep tissues, rendering topical treatments insufficient. The widespread clinical reliance on antibiotics has not only accelerated bacterial resistance but also demonstrated limited efficacy against inherently resistant strains, creating significant hurdles in anti-infective therapy. To address these challenges, we developed a near-infrared (NIR)-responsive nanoplatform via a biomineralization strategy, integrating ytterbium ions (Yb3+) with the photothermal agent indocyanine green (ICG). Benefiting from the unique biological properties of Yb3+, the Yb-BSA@ICG nanoparticles (NPs) achieved a remarkable 6.19 log10 reduction in the viability of multidrug-resistant Pseudomonas aeruginosa (MDR P. aeruginosa) at 48 °C. This mild-temperature photothermal antibacterial approach effectively circumvents the hyperthermia-associated tissue damage commonly linked to conventional photothermal agents. Mechanistic studies further revealed that Yb-BSA@ICG NPs exert their antibacterial effects by inhibiting bacterial respiratory chain complex I activity, reducing the NAD+/NADH ratio and inducing reductive stress. These perturbations disrupt bacterial energy metabolism, which in turn downregulates the expression of heat shock protein (HSP) and diminishes the intrinsic heat tolerance of bacteria, ultimately driving irreversible bacterial cell death. Notably, in a murine model of MDR P. aeruginosa-induced IRIs, Yb-BSA@ICG NPs not only improved the survival rate of infected mice by 50% but also accelerated wound healing by 46.46%. This work advances our understanding of photothermal antibacterial mechanisms and offers a promising strategy for managing deep-seated bacterial infections associated with implanted medical devices.
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