Introduction Diabetic wounds present major healing challenges due to chronic inflammation and oxidative stress. Conventional antioxidants like curcumin are limited by poor solubility and bioavailability. Methods We developed iron-curcumin-coordinated nanoparticles (Fe-Cur-P) to harness curcumin's antioxidant effects while improving its solubility and biocompatibility via iron coordination. The nanoparticles were characterized for size, drug loading, and pH-responsive release of carboxy-PTIO (a nitric oxide scavenger). Antioxidant activity was evaluated using DPPH·, ABTS+·, and methylene blue assays. In vitro anti-inflammatory effects were assessed in LPS-stimulated RAW 264.7 macrophages by measuring apoptosis and cytokine expression. In vivo efficacy was tested in a diabetic mouse wound model, with wound closure rate, histology, and immunohistochemistry analyzed. Results The Fe-Cur-P nanoparticles exhibited a uniform size (9.8 ± 0.6 nm) with 21.31% drug loading and enabled pH-responsive carboxy-PTIO release in acidic wound environments. They potently scavenged reactive oxygen and nitrogen species in multiple antioxidant assays. In RAW 264.7 macrophages, Fe-Cur-P reduced LPS-induced apoptosis and significantly suppressed pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α, and COX-2. In diabetic mice, Fe-Cur-P accelerated wound closure (93.5% ± 2.4% by day 14), promoted vascularization and collagen deposition, and upregulated TGF-β while attenuating inflammation, outperforming both untreated controls and free curcumin. Discussion Iron-curcumin-coordinated nanoparticles effectively combine enhanced curcumin bioavailability with targeted antioxidant and anti-inflammatory activities, demonstrating significant therapeutic potential for diabetic wound healing. This nanoplatform offers a promising strategy to address the multifactorial impairments in chronic wounds.
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