Zinc Oxide Particles Catalytically Generate Nitric Oxide from Endogenous and Exogenous Prodrugs

Yang, Tao; Fruergaard, Anne Sofie; Winther, Anna K.; Zelikin, Alexander N.

doi:10.1002/smll.201906744

Cited by 30 publications

(29 citation statements)

References 42 publications

(37 reference statements)

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“…There are various strategies to administer additional NO to the body; some of these are early stage technologies, while others have made it to the clinics. [ 26 ] NO can be introduced via catalytic generation using enzymes or enzymes mimics with NO donors endogenously present in the body, [ 26,81,82 ] as well as through the delivery of exogenous NO‐releasing species [ 83 ] (Figure 1). Exogenous NO donors have been synthesized and published in great numbers, and several have been translated to the clinic (although, with rare exceptions, not for the treatment of viral diseases).…”

Section: No‐based Therapies To Fight Viral Infectionsmentioning

confidence: 99%

Nitric Oxide to Fight Viral Infections

2021

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Coronavirus disease 2019 (COVID‐19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) that has quickly and deeply affected the world, with over 60 million confirmed cases. There has been a great effort worldwide to contain the virus and to search for an effective treatment for patients who become critically ill with COVID‐19. A promising therapeutic compound currently undergoing clinical trials for COVID‐19 is nitric oxide (NO), which is a free radical that has been previously reported to inhibit the replication of several DNA and RNA viruses, including coronaviruses. Although NO has potent antiviral activity, it has a complex role in the immunological host responses to viral infections, i.e., it can be essential for pathogen control or detrimental for the host, depending on its concentration and the type of virus. In this Essay, the antiviral role of NO against SARS‐CoV, SARS‐CoV‐2, and other human viruses is highlighted, current development of NO‐based therapies used in the clinic is summarized, existing challenges are discussed and possible further developments of NO to fight viral infections are suggested.

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Section: No‐based Therapies To Fight Viral Infectionsmentioning

confidence: 99%

Nitric Oxide to Fight Viral Infections

2021

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“…In such a case, endogenous substrates can be envisioned to provide basal level NO, whereas exogenous NO prodrugs can be used as supplements, to enhance NO levels when needed. The first few reports that present such opportunities (using metallic particles) appear to be promising, [78,86,90] and this avenue of research appears to be rewarding. Understanding the catalytic mechanisms of enzyme mimics for NO release, for example using density functional theory calculations, [119,120] will provide insights into substrate selectivity.…”

Section: Discussionmentioning

confidence: 99%

“…[87][88][89] In our recent work, we discovered that ZnO particles mimicked the activities of β-galactosidase and glutathione peroxidase, and catalyzed both exogenous (β-gal-NONOate) and endogenous (GSNO) NO donors to generate NO. [90] We achieved physiologically relevant NO levels, ranging from 0.1 µM to 2.2 µM, by simply modulating the concentrations of GSNO and ZnO. After 6-month incubation in PBS, ZnO particles preserved their catalytic potency, which is highly beneficial towards long-term biomedical applications.…”

Section: Other Metalsmentioning

confidence: 99%

Enzyme Mimics for the Catalytic Generation of Nitric Oxide from Endogenous Prodrugs

Yang

Zelikin

Chandrawati

2020

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The highly diverse biological roles of nitric oxide (NO) in both physiological and pathophysiological processes have prompted great interest in the use of NO as a therapeutic agent in various biomedical applications. NO can exert either protective or deleterious effects depending on its concentration and the location where it is delivered or generated. This double-edged attribute, together with the short half-life of NO in biological systems, poses a major challenge to the realization of the full therapeutic potential of this molecule. Controlled release strategies show an admirable degree of precision with regards to the spatiotemporal dosing of NO but are disadvantaged by the finite NO deliverable payload. In turn, enzyme-prodrug therapy techniques afford enhanced deliverable payload but are troubled by the inherent low stability of natural enzymes, as well as the requirement to control pharmacokinetics for the exogenous prodrugs. The past decade has seen the advent of a new paradigm in controlled delivery of NO, namely localized bioconversion of the endogenous prodrugs of NO, specifically by enzyme mimics. These early developments are presented, successes of this strategy are highlighted, and possible future work on this avenue of research is critically discussed.

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“…The NO release profiles showed that the release rate sustained up to 5 days with good thrombo-resistant effect. As thrombus involves the formation of fibrin and activation of platelets, Yang et al proposed a novel concept to integrate anti-coagulant agent bivalirudin (BVLD) and NO as a bulk synergetic modification on surface coating (Yang et al, 2020b ). BVLD was covalently connected with the primary amine groups on plasma polymerized allylamine (PPAm)-coated surface, and then the coating was immersed in basic solution under high-pressure NO gas to form a NONOate-like bulk depot.…”

Section: No-releasing Coatingsmentioning

confidence: 99%

Nitric Oxide-Producing Cardiovascular Stent Coatings for Prevention of Thrombosis and Restenosis

Rao

Bei

Yang

et al. 2020

Front. Bioeng. Biotechnol.

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Cardiovascular stenting is an effective method for treating cardiovascular diseases (CVDs), yet thrombosis and restenosis are the two major clinical complications that often lead to device failure. Nitric oxide (NO) has been proposed as a promising small molecule in improving the clinical performance of cardiovascular stents thanks to its anti-thrombosis and anti-restenosis ability, but its short half-life limits the full use of NO. To produce NO at lesion site with sufficient amount, NO-producing coatings (including NO-releasing and NO-generating coatings) are fashioned. Its releasing strategy is achieved by introducing exogenous NO storage materials like NO donors, while the generating strategy utilizes the in vivo substances such as S-nitrosothiols (RSNOs) to generate NO flux. NO-producing stents are particularly promising in future clinical use due to their ability to store NO resources or to generate large NO flux in a controlled and efficient manner. In this review, we first introduce NO-releasing and-generating coatings for prevention of thrombosis and restenosis. We then discuss the advantages and drawbacks on releasing and generating aspects, where possible further developments are suggested.

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Zinc Oxide Particles Catalytically Generate Nitric Oxide from Endogenous and Exogenous Prodrugs

Cited by 30 publications

References 42 publications

Nitric Oxide to Fight Viral Infections

Nitric Oxide to Fight Viral Infections

Enzyme Mimics for the Catalytic Generation of Nitric Oxide from Endogenous Prodrugs

Nitric Oxide-Producing Cardiovascular Stent Coatings for Prevention of Thrombosis and Restenosis

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