Abstract ▼ AI-Helper

In recent decades, nitric oxide (NO) has gained much attention as a novel therapeutic agent for the local treatment of infected wounds and cancer due to not only its potent efficacy but also its minimized off-target side effects. However, since NO is a gaseous and easily degradable molecule, develop...

In recent decades, nitric oxide (NO) has gained much attention as a novel therapeutic agent for the local treatment of infected wounds and cancer due to not only its potent efficacy but also its minimized off-target side effects. However, since NO is a gaseous and easily degradable molecule, development of NO-based formulations and efficient delivery of sufficient NO to the target sites are still challenging. Although several NO-releasing nanoparticles have been developed to treat infected wounds and cancer, limited success has been achieved owing to the poor delivery efficiency of NO resulted from the low NO-loading or short duration time of NO release. Herein, to overcome these limitations, NO donor-poly(lactic-co-glycolic acid) (PLGA) conjugates were newly synthesized, and nanoparticles were fabricated using the NO donor-PLGA conjugates. By grafting hydrophilic NO donor to the hydrophobic PLGA, loss of NO during nanoparticle fabrication processes was prevented, resulting in successful fabrication of sufficient NO-loaded nanoparticle formulations. In this study, S-nitrosoglutathione (GSNO)-conjugated PLGA nanoparticles (GPNPs) and albumin-coated linear polyethyleneimine diazeniumdiolate (LP/NO)-conjugated PLGA nanoparticles (Alb-PLP/NO NPs) were prepared for the treatment of infected wounds and skin cancer, respectively. The potent therapeutic effects of these formulations were demonstrated in a series of experiments, and the results suggest that GPNPs and Alb-PLP/NO NPs could be promising therapeutics for the treatment of infected cutaneous wounds and skin cancer.

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