Nitric oxide-releasing albumin nanoclusters facilitate healing of methicillin-resistant Staphylococcus aureus-infected cutaneous wounds

Purpose: Although nitric oxide (NO)-releasing nanoparticles have garnered significant attention owing to their potent antibacterial effects against methicillin-resistant Staphylococcus aureus(MRSA) and direct promotion of wound healing, the majority of NO-releasing nanoparticles are composed of synthetic polymers or inorganic materials, which may lead to unfavorable effects in the body. To overcome this limitation, we developed NO-releasing albumin nanoclusters (NO/ANCs) using bovine serum albumin, a fully biocompatible endogenous material. Methods: NO/ANCs were fabricated by incorporating diethylenetriamine diazeniumdiolate (DT/NO) into albumin nanoclusters via electrostatic interactions, followed by glutaraldehyde crosslinking between the albumin molecules. The antibacterial effects of the NO/ANCs were investigated using the LIVE/DEAD® BacLight™ bacterial viability kit. The enhanced wound healing and in vivo antibacterial effects were evaluated in a mouse model of MRSA-challenged full-thickness wounds. Results: NO/ANCs were successfully fabricated and could release NO for more than 17 h. NO/ANCs demonstrated enhanced in vitro antibacterial effects and exhibited improved in vivo antibacterial and wound-healing effects in a mouse model of MRSA-challenged full-thickness wounds. Conclusion: NO/ANCs could be a promising formulation for the treatment of MRSA-infected cutaneous wounds.