Vitamin K1-Loaded Poly(Lactic-Co-Glycolic Acid)-Polyethylenimine Nanoparticles Promote Diabetic Wound Healing through FSP1-Dependent Suppression of Ferroptosis
8 affiliations
- 1Center for Tissue Engineering and Stem Cell Research, Translation Medicine Research Center, Guizhou Biomanufacturing Laboratory, Guizhou Medical University, Guiyang, Guizhou, China.
- 2Key Laboratory of Emergency and Trauma of Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, Department of Wound Repair, The First Affiliated Hospital, Hainan Medical University, Haikou, Hainan, China.
- 3Department of Pharmacology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, Guizhou, China.
- 4Center of Wound Repair and Regeneration, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
- 5Department of Wound Repair, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
- 6Cixi Biomedical Research Institute, Wenzhou Medical University, Ningbo, Zhejiang, China.
- 7The State Key Laboratory of Functions and Applications of Medicinal Plants and School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, Guizhou, China.
- 8State Key Laboratory of Flexible Electronics (LoFE) and Institute of Advanced Materials (IAM), School of Physical and Mathematical Sciences, Nanjing Tech University (NanjingTech), Nanjing, Jiangsu, China.
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 Fe²⁺ 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.
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BibTeX
@article{chen2026vitamin,
title = {{Vitamin K1-Loaded Poly(Lactic-Co-Glycolic Acid)-Polyethylenimine Nanoparticles Promote Diabetic Wound Healing through FSP1-Dependent Suppression of Ferroptosis}},
author = {Hongjin Chen and Yiying Chen and Shaowen Cheng and Feiyue Zhao and Kaikai Fan and Sihan Chen and Ying Zhang and Zaijing Liu and Su Wang and Mingzheng Yang and Jiale Song and Xingjie Wu and Jian Wang and Dongliang Yang and Yingnan Song and Xiong Chen},
journal = {Research (Washington, D.C.)},
year = {2026},
month = oct,
doi = {10.34133/research.1469},
url = {https://europepmc.org/article/PMC/PMC13716989},
note = {CC BY},
}
RIS
TY - JOUR
TI - Vitamin K1-Loaded Poly(Lactic-Co-Glycolic Acid)-Polyethylenimine Nanoparticles Promote Diabetic Wound Healing through FSP1-Dependent Suppression of Ferroptosis
AU - Hongjin Chen
AU - Yiying Chen
AU - Shaowen Cheng
AU - Feiyue Zhao
AU - Kaikai Fan
AU - Sihan Chen
AU - Ying Zhang
AU - Zaijing Liu
AU - Su Wang
AU - Mingzheng Yang
AU - Jiale Song
AU - Xingjie Wu
AU - Jian Wang
AU - Dongliang Yang
AU - Yingnan Song
AU - Xiong Chen
PY - 2026
DA - 2026/10/29
JO - Research (Washington, D.C.)
DO - 10.34133/research.1469
UR - https://europepmc.org/article/PMC/PMC13716989
AB - 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 Fe²⁺ 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.
SN - 2639-5274
ER -