Work

Vitamin K1-Loaded Poly(Lactic-Co-Glycolic Acid)-Polyethylenimine Nanoparticles Promote Diabetic Wound Healing through FSP1-Dependent Suppression of Ferroptosis

Year: 2026

Type: article

Abstract: Impaired healing in diabetic wounds presents a major clinical challenge, driven by persistent oxidative stress and dysregulated cellular responses. Herein, a poly(lactic-co-glycolic acid)-polyethylenimine (PLGA-PEI)-based nanoplatform for the sustained delivery of vitamin K1 (VK1) was developed to enhance diabetic wound healing through ferroptosis suppression involving ferroptosis suppressor protein 1 (FSP1). The formulated PLGA-PEI-VK1 nanoparticles exhibited a relatively uniform size distribution, sustained VK1 release, good hemocompatibility, and enhanced antioxidant activity. Network pharmacology analysis suggested that VK1-associated targets were closely related to redox regulation, cell migration, and ferroptosis-associated processes. In vitro, PLGA-PEI-VK1 nanoparticles protected L929 fibroblasts from advanced glycation end products-induced injury; enhanced cell proliferation and migration; attenuated reactive oxygen species accumulation, intracellular Fe 2+ overload, and lipid peroxidation; restored antioxidant capacity; and increased FSP1 expression. In a diabetic mouse model, PLGA-PEI-VK1 nanoparticles significantly accelerated wound closure and improved tissue regeneration and matrix remodeling, supporting its therapeutic potential in vivo. Mechanistically, molecular docking, cellular thermal shift assay, and molecular dynamics simulations supported an interaction between VK1 and FSP1. Furthermore, pharmacological inhibition of FSP1 markedly impaired the anti-ferroptotic effects of PLGA-PEI-VK1, supporting an important role for FSP1 in VK1-dependent ferroptosis suppression. These findings demonstrate that PLGA-PEI-mediated delivery of VK1 promotes diabetic wound repair, at least in part, through FSP1-associated suppression of ferroptosis and provide a potential nanotherapeutic strategy for diabetic wound management.

Source: Research

DOI: 10.34133/research.1469