The potential of nitric oxide releasing therapies as antimicrobial agents

Abstract

Nitric oxide (NO) is a short-lived, diatomic, lipophilic gas that plays an integral role in defending against pathogens. Among its many functions are involvement in immune cell signaling and in the biochemical reactions by which immune cells defend against bacteria, fungi, viruses and parasites. NO signaling directs a broad spectrum of processes, including the differentiation, proliferation, and apoptosis of immune cells. When secreted by activated immune cells, NO diffuses across cellular membranes and exacts nitrosative and oxidative damage on invading pathogens. These observations led to the development of NO delivery systems that can harness the antimicrobial properties of this evanescent gas. The innate microbicidal properties of NO, as well as the antimicrobial activity of the various NO delivery systems, are reviewed.

Figure 1. Chemical structure of sodium nitrite (A), diazeniumdiolate bound to an amine group (B) and S-Nitrosothiols group (C).

Figure 2. (A) Schematic of NO-np synthesis. When combined the components of the silica hydrogel form a gel. As the gel dries it spontaneously breaks into nanoparticles. The heat from the drying process converts NO from nitrite. (B) TEM of NO-np. The scale bars represent 100 nm. The top scale bar represents the top right inset and the bottom scale bar represents the remaining insets. Reproduced with permission from Cabrales et al.