Nitric Oxide (NO)-Releasing Macromolecules: Rational Design and Biomedical Applications

Abstract

Nitric oxide (NO) has been recognized as a ubiquitous gaseous transmitter and the therapeutic potential has nowadays received increasing interest. However, NO cannot be easily directly administered due to its high reactivity in air and high concentration-dependent physiological roles. As such, a plethora of NO donors have been developed that can reversibly store and release NO under specific conditions. To enhance the stability and modulate the NO release profiles, small molecule-based NO donors were covalently linked to polymeric scaffolds, rendering them with multifunctional integration, prolonged release durations, and optimized therapeutic outcomes. In this minireview, we highlight the recent achievements of NO-releasing macromolecules in terms of chemical design and biomedical applications. We hope that more efforts could be devoted to this emerging yet promising field.

Nitric oxide and viral infection: Recent developments in antiviral therapies and platforms

“…Similarly, NO donors such as SNAP have seen extensive evaluation in vitro at treatment ranges from 100–400 µM with reports of negligible cytotoxicity against coxsackievirus, HSV 1, SARS, influenza virus, and vesicular stomatitis virus [64 , 70 , 120 , 122 , 149] . However, the current lack of IC50 data for many NO donors presents significant challenges in the clinical translation of NO-based therapies in addition to other overarching issues such as drug solubility, stability, and trafficking in vivo [150 , 151] .…”

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

“…Polymer represents an efficient platform for NO loading. Polymeric NO donors formed by covalently conjugation or physically encapsulating small molecular-based NO donors to polymer platforms have proven to have excellent NO storage stability, prolonged NO release and optimized pharmacokinetics [38]. To date, various polymer-based NO releasing materials such as nanoparticles, nanofibers, coatings, and hydrogels have been prepared, which have shown great potential for antibacterial applications.…”

“…Furthermore, NO releasing moieties were incorporated with different scaffolds to be applied in many conditions. Polymeric materials can be easily modified and made into various structures, representing powerful scaffolds for NO loading, which can also enhance the stability of NO donors and modulate the NO release profiles [38]. Many polymeric NO releasing materials have been developed for antibacterial application, which demonstrate more significant antibacterial effects than conventional antimicrobial agents while avoiding resistance [39], especially on bacteria in the form of biofilms.…”

Engineering Metal–Organic Frameworks (MOFs) for Controlled Delivery of Physiological Gaseous Transmitters

“…As such, it is of crucial importance to develop NO-releasing materials capable of delivering NO to specific pathological sites and releasing NO on-demand with a proper concentration. In this regard, much effort has been dedicated to various NO-releasing small molecules and nanovectors, including organic-inorganic hybrid materials, macromolecular assemblies, and so on [ 20 , 21 ]. Recently, with the rapid development of MOFs, the high porosity, large surface area, and easy structural adjustment make them promising candidates for NO delivery [ 22 ].…”