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

TY - JOUR

T1 - Zinc Oxide Particles Catalytically Generate Nitric Oxide from Endogenous and Exogenous Prodrugs

AU - Yang, Tao

AU - Fruergaard, Anne Sofie

AU - Winther, Anna K.

AU - Zelikin, Alexander N.

AU - Chandrawati, Rona

PY - 2020/7/1

Y1 - 2020/7/1

N2 - Nitric oxide (NO) is a potent biological molecule that contributes to a wide spectrum of physiological processes. However, the full potential of NO as a therapeutic agent is significantly complicated by its short half-life and limited diffusion distance in human tissues. Current strategies for NO delivery focus on encapsulation of NO donors into prefabricated scaffolds or an enzyme-prodrug therapy approach. The former is limited by the finite pool of NO donors available, while the latter is challenged by the inherent low stability of natural enzymes. Zinc oxide (ZnO) particles with innate glutathione peroxidase and glycosidase activities, a combination that allows to catalytically decompose both endogenous (S-nitrosoglutathione) and exogenous (β-gal-NONOate) donors to generate NO at physiological conditions are reported. By tuning the concentration of ZnO particles and NO prodrugs, physiologically relevant NO levels are achieved. ZnO preserves its catalytic property for at least 6 months and the activity of ZnO in generating NO from prodrugs in human serum is demonstrated. The ZnO catalytic activity will be beneficial toward generating stable NO release for long-term biomedical applications.

AB - Nitric oxide (NO) is a potent biological molecule that contributes to a wide spectrum of physiological processes. However, the full potential of NO as a therapeutic agent is significantly complicated by its short half-life and limited diffusion distance in human tissues. Current strategies for NO delivery focus on encapsulation of NO donors into prefabricated scaffolds or an enzyme-prodrug therapy approach. The former is limited by the finite pool of NO donors available, while the latter is challenged by the inherent low stability of natural enzymes. Zinc oxide (ZnO) particles with innate glutathione peroxidase and glycosidase activities, a combination that allows to catalytically decompose both endogenous (S-nitrosoglutathione) and exogenous (β-gal-NONOate) donors to generate NO at physiological conditions are reported. By tuning the concentration of ZnO particles and NO prodrugs, physiologically relevant NO levels are achieved. ZnO preserves its catalytic property for at least 6 months and the activity of ZnO in generating NO from prodrugs in human serum is demonstrated. The ZnO catalytic activity will be beneficial toward generating stable NO release for long-term biomedical applications.

KW - enzyme mimics

KW - nitric oxide

KW - S-nitrosoglutathione

KW - zinc oxide

KW - β-gal-NONOate

UR - http://www.scopus.com/inward/record.url?scp=85080871253&partnerID=8YFLogxK

U2 - 10.1002/smll.201906744

DO - 10.1002/smll.201906744

M3 - Journal article

C2 - 32141238

AN - SCOPUS:85080871253

SN - 1613-6810

VL - 16

JO - Small

JF - Small

IS - 27

M1 - 1906744

ER -