Nitric oxide (NO) is a potent biological molecule that contributes to a wide spectrum of physiological processes. However, the full potential of NO as therapeutic agents 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. This work provides the first report of 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. 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 towards generating stable NO release for long-term biomedical applications.
Adaptable behavior such as triggered disintegration affords a broad scope and utility for (bio)materials in diverse applications in materials science and engineering. The impact of such materials continues to grow due to the increased importance of environmental considerations as well as the increased use of implants in medical practices. However, examples of such materials are still few. In this work, we engineer triggered liquefaction of hydrogel biomaterials in response to internal, localized heating, mediated by near-infrared light as external stimulus. This adaptable behavior is engineered into the readily available physical hydrogels based on poly(vinyl alcohol), using gold nanoparticles or an organic photothermal dye as heat generators. Upon laser light irradiation, engineered biomaterials underwent liquefaction within seconds. Pulsed laser light irradiation afforded controlled, on-demand release of the incorporated cargo, successful for small molecules as well as proteins (enzymes) in their biofunctional form.
Nanozymes can mimic the activities
of diverse enzymes, and this
ability finds applications in analytical sciences and industrial chemistry,
as well as in biomedical applications. Among the latter, prodrug conversion
mediated by nanozymes is investigated as a step toward site-specific
drug synthesis, to achieve localized therapeutic effects. In this
work, we investigated a ceria nanozyme as a mimic to phosphatase,
to mediate conversion of phosphate prodrugs into corresponding therapeutics.
To this end, the substrate scope of ceria as a phosphatase mimic was
analyzed using a broad range of natural phosphor(di)esters and pyrophosphates.
Knowledge of this scope guided the selection of existing phosphate
prodrugs that can be converted by ceria into the corresponding therapeutics.
“Extended scaffold phosphates” were engineered using
self-immolative linkers to accommodate a prodrug design for amine-containing
drugs, such as monomethyl auristatin E. Phosphate prodrugs masked
activity of the toxin, whereas prodrug conversion mediated by the
nanozyme restored drug toxicity, which was validated in mammalian
cell culture. The main novelty of this work lies in the rational pairing
of the ceria nanozyme with the existing and the de novo designed “extended scaffold” phosphate prodrugs toward
their use in nanozyme–prodrug therapy based on the defined
nanozyme substrate scope.
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