Application Progress of Plant-derived Exosome-like Nanoparticles in Diabetic Ulcers

Diabetes foot ulcers (DFU) is a serious complication of diabetes with high morbidity and mortality. The existing treatment methods have bottlenecks such as large trauma, high cost, and long recovery period. Plant derived extracellular vesicle like nanoparticles (PENPs) have become a novel candidate strategy for DFU treatment due to their natural low immunogenicity, high content of active ingredients such as polyphenols and miRNA, easy large-scale extraction, and good biocompatibility. This article systematically reviews the core mechanisms by which PENPs regulate DFU healing, including exerting anti-inflammatory and antioxidant effects by activating the Nrf2/HO-1 pathway, regulating the gut microbiota immune axis to improve systemic metabolism, promoting angiogenesis through glycolysis reprogramming and PI3K/Akt pathways, regulating insulin signaling to improve glucose metabolism, and directly promoting accelerated proliferation, migration, and re epithelialization of keratinocytes and fibroblasts; Simultaneously reviewing the research progress of 9 types of PENPs, including red onions, lemons, ginseng, and wheat, in cell or animal models, confirming their multi-target healing promoting activity. This article provides theoretical and experimental basis for expanding the field of extracellular vesicle therapy and developing safe and effective natural biological treatment strategies for DFU.