State-of-the-Art and Perspectives for Nanomaterials Combined with Nitric Oxide Donors: From Biomedical to Agricultural Applications

Abstract

The free radical nitric oxide (NO) is a signaling molecule that controls several important physiological and pathophysiological processes in mammals and in plants. In humans, the biological impacts of NO include, but are not limited to, key roles in cardiovascular, neurological, immunological, respiratory, and reproductive systems. In plants, NO modulates plant growth and development with important roles in plant defense against biotic and abiotic stress conditions. However, the administration of exogenous NO donors still faces limitations, mainly due to their instability and lack of bioavailability in the biological system. Recently, the combination of nanomaterials with NO donors has been extensively explored as a promising strategy to tailor the spatiotemporal release of therapeutic amounts of NO. Nanoscience offers smart approaches to deliver NO on demand for a particular application. Although this strategy has shown promising results, the combination of NO donors with nanomaterials is still limited to scientific studies and is less explored in agricultural applications compared with biomedical research. The current review summarizes the impact of NO and NO donors in biomedical research and agricultural applications and emphasizes the recent progress in the combination of nanotechnology and NO donors. The advantages, challenges, and drawbacks of this strategy are discussed in light of inspiring research on this exciting topic, aiming to translate these innovations into clinical/practical settings.

Antimicrobial Effects of Nitric Oxide against Plant Pathogens

“…The use of NO-releasing nanomaterials has the potential to increase their internalization into plant tissue and further enhance NO's antimicrobial efficacy, and represents a promising direction of future work. 33 Treatment of Botrytis cinerea-Infected Tomato Fruit. Botrytis cinerea has a wide range of infection sites, including the leaves, stems, flowers, and fruits of plants, and can infect plants throughout their development process.…”

“…The NO donors with the shortest half-lives (i.e., PAPA/NO and SPER/NO) required the greatest concentrations (i.e., larger MICs) to achieve inhibition of bacterial growth; however, similar MBCs (500–1000 μg mL –1 ) were observed for the NO donors with both the shortest and longest (i.e., GSNO and DETA/NO) NO-release half-lives. The higher concentrations of NO needed from the faster NO-releasing systems suggest a more rapid burst release of NO may not effectively inhibit bacterial growth or lead to eradication, likely due to NO release occurring prior to the NO donor reaching the bacteria and the short diffusion distance of NO . While the NO donors with longer half-lives of NO release effectively inhibited bacterial growth at low concentrations, complete eradication was not achieved and the bacteria were able to grow back, as the lower amounts of NO released toward the end of the release profile are likely unable to exert substantial oxidative and nitrosative stress needed to eradicate the bacteria.…”

“…This treatment led to a 92% decrease in bacterial viability compared to the control, suggesting the promise of utilizing MD3 as a treatment for black speck disease and controlling bacterial infection of tomato plants. The use of NO-releasing nanomaterials has the potential to increase their internalization into plant tissue and further enhance NO’s antimicrobial efficacy, and represents a promising direction of future work …”

“…Exogenous NO has been utilized to promote plant defense against pathogens. Fumigation with NO gas was shown to control insects in fresh produce, including the codling moth in apples, the spotted wing drosophila in strawberries, and aphids in lettuce. − Due to the high reactivity and short half-life (3–5 s) of NO gas, chemical NO donors have been developed to store and controllably release NO for both biomedical and agricultural applications. − Postharvest treatment of tomato fruits with the NO donor sodium nitroprusside (SNP) and preharvest treatment of tomato plants with l -arginine, a precursor of NO, were shown to both enhance the resistance of the fruits against B. cinerea invasion and promote the activity of enzymes involved in plant defense. , Similarly, immersion of pitaya fruit and apples in SNP solutions reduced infection by the fungi Colletotrichum gloeosporioides and Alternaria alternata, respectively. , Sodium nitroprusside also inhibited the germination of Penicillium expansum spores in vitro, decreasing their virulence to apple fruit .…”

Hyaluronic Acid-Coated Silica Nanoparticles for Targeted Delivery of Nitric Oxide to Cancer Cells

“…Indeed, resistance to NO treatment has yet to be observed. − Treatment with NO in its gaseous form has associated limitations, requiring high clinical oversight due to potential adverse effects (e.g., methemoglobinemia) and the availability of and hazards associated with pressurized gas cylinders. Current NO research for cancer applications has emphasized the importance of developing stable, solution-phase NO donors that will allow for the controlled delivery of NO to the tumor. − …”