Multifunctional Spiked Polydopamine Nanoplatform via Photothermal Antibacterial and Macrophage Reprogramming for the Treatment of Infected Diabetic Wounds

Recurrent bacterial infections and sustained inflammation remain the principal barriers to the healing of infected diabetic wounds. Although functional nanoparticles integrated with photothermal therapy (PTT) have emerged as promising alternatives to conventional treatments, their clinical translation is limited by pronounced pro-inflammatory side effects. In particular, the reactive oxygen species (ROS) burst induced by the Fenton-like reactions of metal-based photothermal agents can exacerbate oxidative stress and tissue damage. To overcome this limitation, we engineered a hedgehog-like manganese-doped polydopamine nanoplatform (MnPDA) that couples potent photothermal antibacterial activity with intrinsic anti-inflammatory functionality. Upon near-infrared irradiation, MnPDA enables efficient heat generation and structural bacteria–nanoparticle interactions, achieving broad-spectrum eradication of planktonic bacteria, disruption of biofilms, and clearance of intracellular pathogens. Simultaneously, manganese incorporation endows MnPDA with stronger ROS-scavenging capability, attenuating PTT-associated oxidative damage. By reducing excessive ROS and reprogramming macrophages toward a pro-regenerative phenotype, MnPDA alleviates chronic inflammation and restores immune homeostasis within the wound microenvironment. This integrated strategy achieves synchronized infection control and inflammatory modulation, effectively breaking the infection–inflammation vicious cycle and accelerating wound closure in diabetic models. Collectively, MnPDA-mediated PTT represents a multifunctional therapeutic platform for advanced management of infected diabetic wounds.