The role of nanoparticles in the treatment of diabetic foot ulcers: mechanisms, delivery platforms, translational challenges, and future directions

Diabetic foot ulcers (DFUs) are complex chronic wounds characterized by persistent infection, inflammation, oxidative stress, impaired angiogenesis, and delayed tissue regeneration. Nanoparticle-based systems have emerged as promising therapeutic platforms because they can provide antimicrobial, anti-inflammatory, antioxidant, and proangiogenic effects. This review examines recent advances in nanoparticle-integrated platforms for DFU management, including hydrogels, nanofibers, scaffolds, smart dressings, nanoemulsions, and nanogels. These platforms can enhance drug stability, facilitate controlled and sustained release, improve tissue interactions, and support targeted delivery. Preclinical evidence indicates that they can reduce microbial burden, regulate the wound microenvironment, promote angiogenesis and tissue regeneration, and accelerate wound closure. Clinical translation remains limited by potential cytotoxicity, long-term tissue accumulation, variability in nanoparticle synthesis, and the absence of standardized evaluation protocols. Manufacturing scalability, regulatory requirements, high production costs, and limited accessibility in resource-constrained settings present additional barriers. Future research should prioritize long-term safety assessment, standardized manufacturing and evaluation, affordable production, personalized therapies, integration with smart or artificial intelligence-enabled wound-monitoring systems, and combination approaches involving regenerative medicine. Nanoparticle-integrated platforms offer considerable potential for improving DFU management. However, successful clinical application will depend on overcoming existing safety, standardization, regulatory, manufacturing, and affordability challenges.