Nitric Oxide-Releasing Polymeric Materials for Antimicrobial Applications: A Review

Abstract

Polymeric materials releasing nitric oxide have attracted significant attention for therapeutic use in recent years. As one of the gaseous signaling agents in eukaryotic cells, endogenously generated nitric oxide (NO) is also capable of regulating the behavior of bacteria as well as biofilm formation in many metabolic pathways. To overcome the drawbacks caused by the radical nature of NO, synthetic or natural polymers bearing NO releasing moiety have been prepared as nano-sized materials, coatings, and hydrogels. To successfully design these materials, the amount of NO released within a certain duration, the targeted pathogens and the trigger mechanisms upon external stimulation with light, temperature, and chemicals should be taken into consideration. Meanwhile, NO donors like S-nitrosothiols (RSNOs) and N-diazeniumdiolates (NONOates) have been widely utilized for developing antimicrobial polymeric agents through polymer-NO donor conjugation or physical encapsulation. In addition, antimicrobial materials with visible light responsive NO donor are also reported as strong and physiological friendly tools for rapid bacterial clearance. This review highlights approaches to delivery NO from different types of polymeric materials for combating diseases caused by pathogenic bacteria, which hopefully can inspire researchers facing common challenges in the coming ‘post-antibiotic’ era.

Approaches for the inhibition and elimination of microbial biofilms using macromolecular agents

“…5). [87][88][89] Nitric oxide (NO) itself is an endogenous small molecule gasotransmitter, which is involved in a number of normal physiological processes. As a free radical, nitric oxide shows inherent reactivity towards proteins, metabolic enzymes, DNA, and cell surfaces, and as such exhibits broad-spectrum antimicrobial activity through both oxidative and nitrosative processes.…”

“…As a free radical, nitric oxide shows inherent reactivity towards proteins, metabolic enzymes, DNA, and cell surfaces, and as such exhibits broad-spectrum antimicrobial activity through both oxidative and nitrosative processes. 87,179 Furthermore, upon reaction with molecular oxygen and other reactive oxygen species, nitric oxide readily converts into further reactive species such as nitrogen dioxide (NO 2 ), dinitrogen trioxide (N 2 O 3 ) and peroxynitrite (ONOO À ), which also exhibit separate antimicrobial modes of activity. 87,179 Whilst nitric oxide itself is a promising antimicrobial agent, it has a very short half-life in vivo and is challenging to handle and deliver owing to its gaseous nature.…”

Pulp–Dentin Tissue Healing Response: A Discussion of Current Biomedical Approaches

“…However, the molecule has an elevated risk for toxicity by direct application. Therefore, the use of biomaterials to mediate its release is important to ensure the viability of surrounding tissue [96]. NO has been implicated in the modulation of tumor biology with both tumoricidal and tumor-promoting properties.…”

The Role of Reactive Oxygen Species and Nitric Oxide in the Inhibition of Trichophyton rubrum Growth by HaCaT Cells

“…NO, a gaseous immunomodulator with multimechanistic antimicrobial activity, is formed by the oxidation of L-arginine by nitric oxide synthase (NOS) in eukaryotic cells [18]. NO has been reported to have antimicrobial activity against bacteria, fungi, and viruses both in vitro and in vivo [19][20][21]. Its antifungal activities have been reported to delay mycelial growth and conidial germination [22,23].…”