A Photothermally Triggered Nanoplatform for Multidimensional Antibacterial Therapy and Accelerated Healing of...

Bacterial infection and biofilm formation synergistically hinder wound healing by perpetuating inflammation and evading conventional treatments. Monotherapeutic strategies often fail to simultaneously eradicate resilient biofilms and rectify the dysregulated wound microenvironment. To overcome these limitations, we developed a multifunctional and targeted nanoplatform for synergistic antibacterial therapy and immunomodulation.

The smart nanoplatform (CCP-DFO(Fe)) was constructed with a triple-component architecture: a photothermal Cu₇S₄ core pre-loaded with chlorogenic acid (CGA), enveloped by a thermo-responsive poly(N-vinylcaprolactam) (PVCL) shell, and surface-functionalized with deferoxamine-iron (DFO(Fe)) via amide coupling for active bacterial targeting.

The nanoplatform exhibits effective bacterial targeting via DFO(Fe)-mediated siderophore mimicry, enabling preferential accumulation at infection sites. Under NIR irradiation, CCP-DFO(Fe) nanoplatform exhibits efficient photothermal conversion, rapidly elevating the temperature to 44.3 °C within 4 min, which induces the sudden collapse of the PVCL shell from a uniform swollen state to a phase-separated state, leading to shell disruption and consequent exposure of the CGA-loaded Cu₇S₄ nanoparticles (CSC). Under physiological conditions, the CSC nanoplatform gradually releases Cu²⁺ and CGA, which, together with the photothermal effect, synergistically exert potent antibacterial activity. As a result, the nanoplatform achieves highly effective bacterial eradication, reducing the survival rates of both E. coli and S. aureus to below 5%, along with pronounced anti-biofilm activity. Beyond its antibacterial activity, the released CGA further exerts antioxidant and anti-inflammatory effects by scavenging reactive oxygen species and promoting macrophage polarization toward the pro-healing M2 phenotype, thereby facilitating inflammation resolution. In an infected rat wound model, CCP-DFO(Fe) combined with NIR irradiation achieved 98.56 ± 1.08% wound closure by day 14, with nearly complete bacterial eradication, while simultaneously promoting angiogenesis and collagen deposition.

This integrated nanoplatform combines targeted antibacterial activity, biofilm disruption, and inflammation resolution into a single system, demonstrating significant potential for treating infected and chronic wounds.