Tier 3 — preclinical

Nitric Oxide: Physiological Functions, Delivery, and Biomedical Applications

Andrabi SM, Sharma NS, Karan A, Shahriar SMS, Cordon B, Ma B, Xie J
Advanced Science 2023 10(30):e2303259

Bibliography

PubMed
PMID 37632708
PubMed Central
PMC10602574
Funding
Supported by NIH/NIGMS and NIH/NIDCR (Award Nos. R01GM138552, R01DE031272, P30GM127200), CDMRP/PRMRP (FY19 W81XWH2010207), a Nebraska Research Initiative pilot grant (NE LB606), and startup funds from the University of Nebraska Medical Center.
Competing interests
The authors declare no conflict of interest.

Study snapshot

DesignNarrative literature review (not a primary study)
ModelN/A - review of NO donor/carrier systems in preclinical and in vitro models
SampleN/A - review
InterventionN/A - review
DurationN/A - review
EndpointsNO release kinetics/payload from donor-carrier platforms; Antibacterial/wound-healing efficacy of NO-releasing materials; Platelet aggregation/thrombus formation on NO-releasing cardiovascular implants

What the study showed, in plain terms

Nitric oxide (NO) is a gas the body makes to relax blood vessels, fight infection, and help wounds heal, but it disappears within seconds, making it hard to deliver as a medicine. This review surveys the many "NO donor" chemicals and delivery vehicles - nanoparticles, hydrogels, dressings, implant coatings - that scientists have engineered to release NO in a controlled, sustained way at the site of disease.

The authors describe how these NO-releasing platforms are being tested for wound healing, killing antibiotic-resistant bacteria, preventing blood clots on stents and vascular grafts, and starving tumors of blood supply or triggering tumor cell death - highlighting both the promise and the remaining safety/manufacturing hurdles of turning NO into a practical drug.

Key findings

  • NO donors span several chemical classes - nitrates, N-diazeniumdiolates/NONOates, nitrosothiols, furoxans, metal nitrosyl compounds, nitrobenzenes - each with distinct release kinetics and stability
  • Polymeric nanoparticles, dendrimers, liposomes, and stimuli-responsive materials (pH-, light-, enzyme-triggered) improve NO stability, targeting, and sustained release compared to free NO donors
  • NO-releasing scaffolds/coatings accelerate wound healing and angiogenesis, kill gram-positive and gram-negative bacteria (including MRSA) via nitrosative/oxidative stress, and reduce platelet adhesion on vascular implants and stents
  • Micromolar NO concentrations induce apoptosis and inhibit tumor growth (targeted via NO-releasing nanoplatforms and NIR-triggered release), while nanomolar-picomolar concentrations promote angiogenesis and cell survival

What this study can and cannot tell us

Most evidence summarized is preclinical (in vitro/animal), and the review does not systematically grade study quality or clinical translation stage; concentration-dependent, sometimes opposing, effects of NO (e.g., pro- vs anti-tumorigenic) make generalization across applications difficult.

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