Selenium Nanoparticle Microneedle Patches Promote Diabetic Oral Ulcer Healing via Mitophagy

Abstract

Diabetes mellitus (DM) is frequently complicated by refractory oral ulcers, which are characterized by persistent inflammation and impaired healing. We first identified that diabetic oral ulcer tissues exhibit significant selenium deficiency, downregulated SELENBP1 expression, and substantial mitochondrial damage – key factors contributing to the pathogenesis. To address this pathological condition, we developed a sericin-selenium nanoparticle-loaded microneedle patch (Ser-SeNPs@MN) for efficient selenium delivery and targeted therapy of diabetic oral ulcers. The Ser-SeNPs were synthesized using a green sericin-based method, demonstrating enhanced stability and biosafety. The Ser-SeNPs@MN enabled mucosal adhesion and sustained release of Ser-SeNPs, significantly improving selenium bioavailability. In vitro experiments revealed that Ser-SeNPs@MN promoted the expression of SELENBP1 and key selenoproteins (GPX1, GPX2, TXNRD1, TXNRD2), activated PINK1/Parkin-mediated mitophagy, and restored mitochondrial function. Consequently, it suppressed pro-inflammatory responses and facilitated M2 macrophage polarization. In both diabetic oral ulcer and skin wound rat models, Ser-SeNPs@MN accelerated wound closure, enhanced collagen deposition, and promoted angiogenesis. These findings underscore the therapeutic potential of Ser-SeNPs@MN as a multifunctional platform for diabetic wound management through selenium-mediated mitochondrial recovery and immune modulation. Graphical The alternative text for this image may have been generated using AI. The Ser-SeNPs@MN patch is applied topically onto the diabetic oral ulcer or skin wound. Upon application, the microneedle tips penetrate the mucosal or epidermal barrier, dissolving rapidly to release Ser-SeNPs locally. This leads to upregulation of SELENBP1, enhanced selenoprotein production, activation of PINK1/Parkin-mediated mitophagy, promotion of M2 macrophage polarization, and accelerated wound healing