Light-switchable micro-nano platform based on lanthanide-doped Ni-MOF for on-demand drug release and photothermal therapy of diabetic wounds

The hyperglycemic microenvironment in chronic diabetic wounds predisposes them to tissue necrosis, while persistent inflammation impairs the function of reparative cells and disrupts the formation of new tissue, leading to a stagnation of the healing process. Current therapeutic strategies are limited by inefficient drug delivery, inadequate bioavailability, and the inability of single-pharmacology mechanisms to coordinately intervene in the complex pathological network. In this study, we have constructed a light-responsive lanthanide-doped nickel-based metal-organic framework micro-nano platform (Q@NTY/LIG), which achieves synergistic photothermal therapy and photo-controlled drug release for diabetic wounds. This system utilizes Yb 3+ /Tm 3+ -doped NYT-MOF for the in situ and efficient loading of quercetin (Que). Under near-infrared (NIR) irradiation, the excitation of Yb 3+ /Tm 3+ in NYT-MOF generates upconversion luminescence that drives cis-trans isomerization of azobenzene ligands, enabling precise quercetin (Que) release (up to 85%) in the diabetic wound microenvironment. Furthermore, integrating Q@NTY with lignin (LIG) enhances biosafety and imparts a photothermal capability, achieving >99.9% bacterial clearance. Collectively, Que and LIG alleviate oxidative stress, stimulate angiogenesis, and synergistically promote tissue repair. Furthermore, Q@NTY/LIG reprograms the immune microenvironment via downregulating pro-inflammatory factors, upregulating anti-inflammatory factors and chemokines, thereby facilitating M2 macrophage polarization. This NIR-responsive system achieves spatiotemporally precise drug release and synergizes photothermal with pharmacological therapy to address core challenges such as inflammation and bacterial infection, thereby significantly enhancing diabetic wound healing efficiency. This work provides a novel multi-target synergistic delivery strategy for the treatment of chronic diabetic wounds. • NIR-triggered upconversion enables in-situ precise drug release. • Upconversion drives azobenzene isomerization for spatiotemporal release. • Antioxidative, anti-inflammatory and antibacterial actions promote wound healing.