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

Yueying Fan,1,* Jinfu Li,1,* Peng Wang,1,* Yuhuan Peng,1 Chao Yan,1 Xiangyang Li,1 Zhaoxiang Wang,1 Xiao Li,1 Zhanchen He,1 Wenqiang Li,2 Bin Yin,1 Chiyu Jia1 1Center of Burn & Plastic and Wound Healing Surgery, The First Affiliated Hospital of University of South China, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China; 2Guangdong Traditional Medical and Sports Injury Rehabilitation Research Institute, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong 510317, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin Yin; Chiyu Jia, Email [email protected]; [email protected]: 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.Methods: 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.Results: 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.Conclusion: 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. An infographic about treating an infectious wound using CCP-DFO(Fe) under 808 nm NIR. Top section: 808 nm NIR points to CCP-DFO(Fe), followed by three outputs labeled Cu2+, CGA and PTT. The CCP-DFO(Fe) nanoscale platform will be labeled as “targeted antimicrobial” and connected with a plus sign to a balance diagram labeled “anti-inflammatory”. Middle and lower section: a mouse labeled Infectious Wound is shown with a syringe at a wound site. To the right, a skin cross-section is labeled Wound Healing and includes labels CD206, IL-10, TNF-α, IL-6, CD86, Arg-1, α-SMA, CD31 and immune states M1 and M2, with a directional change from M1 toward M2.An infographic of CCP-DFO(Fe) using 808 nm NIR for antibacterial, anti-inflammation and wound healing.Keywords: smart nanoplatform, targeted antibacterial, photothermal therapy, infected wound healing