A programmable NIR-II-activated phase-change nanoplatform for antibacterial therapy and microenvironment remodeling in diabetic chronic wounds.

Abstract

Diabetic chronic wounds remain a major clinical challenge due to persistent oxidative stress, increasing antimicrobial resistance, and dysregulated intercellular communication, which severely limit the efficacy of conventional monotherapies. To address these limitations, we developed a near-infrared II (NIR-II)-activated, thermoresponsive nanotherapeutic platform, CPNPs-Rhein@PCM (CRP), that combines photothermal conversion with on-demand drug release for coordinated infection control and wound microenvironment remodeling. Donor-acceptor-structured conjugated polymer nanoparticles (CPNPs) with high photothermal conversion efficiency (57.8%) function as the photothermal core, while rhein is encapsulated within liposomal phase-change materials (PCM, phase-transition temperature ≈45 °C) to enable precisely regulated thermal release. The resulting nanoplatform exhibits excellent colloidal stability, strong NIR-II absorption, and high drug-loading efficiency (42.5%), enabling rapid and controllable drug release under laser irradiation. Under NIR-II excitation, localized hyperthermia induces PCM phase transition and synchronizes photothermal sterilization with rhein-mediated chemical inhibition. This coordinated activation disrupts bacterial membranes, suppresses biofilm formation, scavenges excessive reactive oxygen species, and promotes macrophage polarization toward the pro-regenerative M2 phenotype, thereby facilitating angiogenesis, endothelial migration, and extracellular matrix remodeling. Transcriptomic analyses further reveal that CRP treatment systematically regulates inflammation, migration, angiogenesis, and tissue repair-related signaling pathways, providing molecular-level evidence for its immunomodulatory and regenerative functions. Both in vitro and in vivo investigations confirm that CRP achieves >99% antibacterial efficiency against Staphylococcus aureus and Escherichia coli, leading to >90% wound closure within 24 h and near-complete wound healing within 16 days in an infected diabetic mouse model, without detectable systemic toxicity. Thus, this study establishes CRP as a nanoplatform that exhibits quantitatively confirmed photothermal-chemical synergistic antibacterial performance. It further regulates macrophage polarization, ROS scavenging and angiogenesis to remodel the diabetic wound microenvironment for efficient tissue regeneration, and highlights its potential for the precision treatment of refractory diabetic chronic wounds.