An NIR-responsive PDA@RES core-shell nanoplatform accelerates chronic wound healing by remodeling mitochondrial homeostasis and reversing cellular senescence

Chronic wound healing remains a significant clinical challenge due to persistent inflammation, oxidative stress, mitochondrial dysfunction, and cellular senescence. A near-infrared (NIR)-responsive polydopamine-resveratrol (PDA@RES) core-shell nanoplatform was developed to address these interconnected pathological mechanisms through synergistic photothermal therapy and drug delivery. The nanoplatform exhibited excellent photothermal conversion capability and demonstrated superior antioxidant and anti-inflammatory effects, effectively scavenging intracellular reactive oxygen species (ROS), restoring mitochondrial membrane potential, and repolarizing macrophages toward a pro-healing phenotype. Mechanistically, the platform activated the AMPK/PGC-1α signaling axis, initiating programmed mitochondrial homeostasis remodeling through enhanced mitophagy and biogenesis, thereby blocking senescence-inducing signals and reversing cellular senescence. The immune microenvironment remodeling subsequently promoted vascular endothelial cell migration and angiogenesis. In diabetic rat models, the NIR-responsive nanoplatform significantly accelerated wound healing by promoting collagen deposition, balancing the immune microenvironment, and facilitating functional vascular regeneration. Notably, the treatment induced nascent hair follicle structures, achieving high-quality regenerative healing rather than scar formation. This study provides an efficient, multi-target synergistic therapeutic strategy for chronic wound healing.