Nanozymes and Glucuronides: Glucuronidase, Esterase, and/or Transferase Activity

Walther, Raoul; Akker, Wouter van den; Fruergaard, Anne Sofie; Zelikin, Alexander N.

doi:10.1002/smll.202004280

Cited by 11 publications

(4 citation statements)

References 24 publications

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“…In turn, for monosubstituted phosphates, the lowest activities are observed on derivatives of primary alcohols (thiamine and thymidine phosphates). This finding supports numerous prior reports on the use of ceria to hydrolyse, e.g., fluorescein diphosphate (phenolic), natural nucleotides (pyrophosphates), and organophosphorous nerve agents. − It also supports the conclusion of our previous publication on the nanozyme mimicry of glucuronidase in which diverse nanozymes (metals, metal oxides, and 1D and 2D materials) were active only against glucuronides of “good leaving group” aglycons (e.g., phenolics). , …”

Section: Resultssupporting

confidence: 89%

“…15−21 It also supports the conclusion of our previous publication on the nanozyme mimicry of glucuronidase in which diverse nanozymes (metals, metal oxides, and 1D and 2D materials) were active only against glucuronides of "good leaving group" aglycons (e.g., phenolics). 28,31 The definition of the substrate scope for the ceria nanozyme offers opportunities to select specific prodrugs that can be used in a "nanozyme prodrug therapy", to achieve localized syntheses of drugs. 28,32 In our prior work, we investigated site-specific drug synthesis using enzyme-containing biomaterials and revealed its potential to, e.g., combat bacterial colonization of surfaces, to generate anticancer agents, and to locally synthesize short-lived radical gaso-transmitter nitric oxide.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Ceria Nanozyme and Phosphate Prodrugs: Drug Synthesis through Enzyme Mimicry

Walther

Huynh

Monge

et al. 2021

ACS Appl. Mater. Interfaces

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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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Section: Resultssupporting

confidence: 89%

Section: ■ Results and Discussionmentioning

confidence: 99%

Ceria Nanozyme and Phosphate Prodrugs: Drug Synthesis through Enzyme Mimicry

Walther

Huynh

Monge

et al. 2021

ACS Appl. Mater. Interfaces

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“…The ratios of Ce 3+ /Ce 4+ were reported to be a decisive factor of different catalytic activities of ceria, including oxidase, [56] peroxidase, [69,70] superoxide dismutase, [64] catalase, [65] haloperoxidase, [71] phosphatase, [50] and glucuronidase. [72] We examined the ratio changes of Ce 3+ /Ce 4+ on the surface of ceria NPs before and after the interaction with GSNO by XPS. The ratio of valence state of Ce 3+ (peaks at 884.2 and 880 eV) and Ce 4+ (peaks at 881.78, 887.92, 897.52 eV) (Figure 4c) was determined to be 0.547.…”

Section: Catalytic Mechanismmentioning

confidence: 99%

Ceria Nanoparticles as an Unexpected Catalyst to Generate Nitric Oxide from S‐Nitrosoglutathione

Luo

Zhou

Gao

et al. 2022

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half-life (<5 s) and diffusion distance (40-200 µm) in vitro and in vivo. [7] In addition, the biological functions of NO are pleiotropic and strongly dependent on its concentrations. At lower concentrations (pm to nm), NO promotes cell survival and proliferation, [8,9] while higher NO concentrations (µm to mm) cause cell apoptosis [10] with potential for anticancer, [11] antibacterial, [12] and antiviral applications. [13] To this end, researchers have developed a number of NO-releasing platforms where NO donors, denoted as substances that transport and release NO upon specific stimulus, are encapsulated into pre-fabricated scaffolds (e.g., silica nanoparticles, polymers, liposomes, hydrogels, and metal-organic frameworks). [8,[14][15][16][17] Even though these platforms have been demonstrated to enable controlled and sustained NO release profiles, [18][19][20] their NO payloads and duration of NO release principally rely on the finite amount of NO donors incorporated. To tackle this issue, NO delivery by catalytic approaches have been developed, which enables in situ continuous NO generation from naturally occurring endogenous NO donors S-nitrosothiols (RSNOs) mediated by catalytic reagents. [21] One of the well-known catalytic approaches for NO generation is the copper-facilitated decomposition of S-nitrosothiols, where transition Cu 2+ is reduced to Cu + by thiolate, and Cu + subsequently reacts with RSNO to release NO and regenerate Cu 2+ . [22] This discovery has led to the development of copper-based materials for NO release from S-nitrosoglutathione (GSNO), [23,24] S-nitrosocysteamine, [25,26] S-nitrosocysteine (CysNO), [27] and S-nitroso-Nacetyl-DL-penicillamine (SNAP). [28] Another representative catalytic agent for NO release is gold nanoparticles. Catalytic gold nanoparticles were reported to catalyze NO release from GSNO, SNAP, and S-nitrosopenicillamine, which was ascribed to the formation of Au-thiolate and the oxidation of Au 0 to Au [1] on the surface of gold nanoparticles. [29,30] Recently, Doverspike et al. [31] reported that zinc oxide particles enhanced NO release from GSNO, and our group [32,33] presented the ability of zinc oxide particles to catalytically decompose both endogenous (GSNO) and exogenous (β-gal-NONOate) donors to generate NO at physiological conditions. Intriguingly, the opposite capability, that is, NO-scavenging capability, of gold nanoparticles, [34] copper nanoparticles, [35] and zinc oxide particles [36,37] in the presence of excessive NO were also reported, which shows the multi-faceted functions of these transition metal nanoparticles.Ceria nanoparticles (NPs) are widely reported to scavenge nitric oxide (NO) radicals. This study reveals evidence that an opposite effect of ceria NPs exists, that is, to induce NO generation. Herein, S-nitrosoglutathione (GSNO), one of the most biologically abundant NO donors, is catalytically decomposed by ceria NPs to produce NO. Ceria NPs maintain a high NO release recovery rate and retain their crystalline structure for at least 4 w...

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“…Enzyme-responsive prodrug strategies allow site-specific release of drug, enabling potentiation of cancer diagnosis and therapy. In recent years, many efforts have been devoted to developing enzyme activated prodrugs by implanting tunable moieties responding to upregulated enzymes at the tumor environment, including matrix metalloproteinase (MMP), − phosphatase, − heparanase, tyrosinase, cathepsin B, − aminopeptidase N, glucuronidase, − glycosidase, , NAD(P)H:quinone oxidoreductase-1 (NQO1), − and nitroreductase (NTR). − NQO1 is a well-known tumor-specific overexpressed cytosolic flavoenzyme , catalyzing the reduction of quinones to fight the intracellular oxidative stress. , Leveraging NQO1 as a triggering button to locally activate prodrugs is practical. Quinone propionic acid has been reported as NQO1 responsive ligands for modification of proteins, chemotherapy drugs, and fluorescent probes. − β-Lapachone possesses a distinct quinone structure and could be converted by NQO1 to release ROS, resulting in unrepaired oxidative DNA lesions and cell death, ,, while developing NQO1-responsive drug delivery systems is still imperative for improving therapeutic index …”

Section: Introductionmentioning

confidence: 99%

Intracellular Enzyme-Responsive Profluorophore and Prodrug Nanoparticles for Tumor-Specific Imaging and Precise Chemotherapy

Pei

Zhou

et al. 2021

ACS Appl. Mater. Interfaces

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Responsive drug delivery systems possess great potential in disease diagnosis and treatment. Herein, we develop an activatable prodrug and fluorescence imaging material by engineering the endogenous NAD(P)-H:quinone oxidoreductase-1 (NQO1) responsive linker. The as-prepared nanomaterials possess the NQO1-switched drug release and fluorescence enablement, which realizes the tumor-specific chemotherapy and imaging in living mice. The enzyme-sensitive prodrug nanoparticles exhibit selectively potent anticancer performance to NQO1-positive cancer and ignorable offtarget toxicity. This work provides an alternative strategy for constructing smart prodrug nanoplatforms with precision, selectivity, and practicability for advanced cancer imaging and therapy.

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Nanozymes and Glucuronides: Glucuronidase, Esterase, and/or Transferase Activity

Cited by 11 publications

References 24 publications

Ceria Nanozyme and Phosphate Prodrugs: Drug Synthesis through Enzyme Mimicry

Ceria Nanozyme and Phosphate Prodrugs: Drug Synthesis through Enzyme Mimicry

Ceria Nanoparticles as an Unexpected Catalyst to Generate Nitric Oxide from S‐Nitrosoglutathione

Intracellular Enzyme-Responsive Profluorophore and Prodrug Nanoparticles for Tumor-Specific Imaging and Precise Chemotherapy

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