Artificial Metalloenzyme‐Based Enzyme Replacement Therapy for the Treatment of Hyperuricemia

Liu, Xinping; Zhang, Zhijun; Zhang, Yan; Guan, Yijia; Liu, Zhen; Ren, Jinsong; Qu, Xiaogang

doi:10.1002/adfm.201602932

Cited by 60 publications

(46 citation statements)

References 64 publications

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“…Following intravenous (i. v.) administration in study model, ESUBFs provided a significantly higher area under the plasma concentration (AUC) and longer circulation half-life (t1/2) compared with free UBF, similar to studies by Xiong H et al [79]. The preparatory security assessment actively exhibited that ESUBFs was acceptable when injected through the parenteral route of administration thus used in emergencies of enzyme replacement for curing enzyme deficit diseases [80].…”

Section: Generation Of Streptavidin-liposomal Conjugates For Targetedmentioning

confidence: 56%

Enzymosomes: A Rising Effectual Tool for Targeted Drug Delivery System

et al. 2017

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The study aims to develop enzymosomes as an emerging novel drug delivery system for site-specific action. Enzymosomes utilises the specific nature of an enzyme, which is binding to a specific substrate at a controlled rate and catalysing product production step. An enzyme is encapsulated by coupling covalently to the surface of liposomes/lipid vesicles to form enzymosomes. Enzymes links through acylation, direct conjugation, physical adsorption, encapsulation methods to prepare enzymosomes with targeted action. Such novel drug delivery systems prove effective drug release and concomitantly reduces undesirable side effects of conventional treatment methods and hence showcase improvement in the long-term therapy of the disease. They are a promising substitute to conventional treatment therapies of gout, antiplatelet activities etc. Enzymosomes are newly designed supramolecular vesicular delivery systems to be useful as a tool in pharmaceutics for the raising of drug targeting and physicochemical properties and hence bioavailability. It shows beneficial effects of drugs with a narrow precision because targeting of these drugs to their site of action improves the drugs overall pharmacodynamics and pharmacokinetic profile. It also minimizes alterations in the normal enzymatic activity, thus enhancing half-life and achieve enzyme activity on targeted sites such as cancerous cells.

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Section: Generation Of Streptavidin-liposomal Conjugates For Targetedmentioning

confidence: 56%

Enzymosomes: A Rising Effectual Tool for Targeted Drug Delivery System

et al. 2017

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“…Some strategies have attempted to co‐deliver CAT‐like nanozymes and UOD into the blood of hyperuricemia animals in which CAT activity was used to reduce the toxic side effects of excess H 2 O 2 produced during UA oxidation. [ 49,50 ] However, the harsh preparation conditions in these strategies may cause the activity of the loaded enzyme to be lost, and adjusting the amount of protein/nanomaterial in the combination is challenging. In comparison, PEG‐ pero ‐nanozysome has both UOD‐like and CAT‐like activities, which may eliminate UA and H 2 O 2 through a cascade reaction by itself, thereby treating hyperuricemia more safely and efficiently.…”

Section: Resultsmentioning

confidence: 99%

A Nanozyme‐Based Artificial Peroxisome Ameliorates Hyperuricemia and Ischemic Stroke

Zhang

Wang

et al. 2020

Adv Funct Materials

167

104

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Artificial peroxisome has drawn a lot of attentions for its usefulness in fabricating protocell system and great potential in treating diseases. However, it is still a significant challenge to prepare a practicable artificial peroxisome to complement multiple and stable functions under physiological condition. Herein, a novel strategy is reported to design an artificial peroxisome using a nanozyme to accommodate multiple enzyme‐like activities that mimics those enzymes in natural peroxisome. The enzymatic active sites are introduced into graphitized moieties on the shell of a hollow carbon nanozyme by doping iron and nitrogen to form Fe–N4 coordination and atomic Fe cluster. With Fe clusters as reversible cofactors and Fe–N4 as prosthetic group, the resulted carbon nanozyme exhibits stable and multiple peroxisomal‐like activities, including catalase, uricase, superoxide dismutase, peroxidase, and oxidase, which is referred as nanozyme‐based artificial peroxisome (pero‐nanozysome). This pero‐nanozysome shows therapeutic effect for treating hyperuricemia and protecting neurons from free radicals generated during ischemic stroke by employing the tandem activities of uricase‐catalase and superoxide‐dismutase‐catalase, respectively. This study indicates that the pero‐nanozysome is a promising candidate to design artificial peroxisome performing in vivo functions.

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“…In the second reaction of the cascade, different artificial, catalytic nanoparticles can be employed to transform H 2 O 2 into •OH, 1 O 2 (singlet oxygen), and •O − 2 (Cho et al, 2019). These catalytic nanoparticles include AuNPs (Zhang et al, 2019), iron oxide (Fan et al, 2012;Duan et al, 2015;Gao et al, 2016;Liu et al, 2018;Naha et al, 2019), silver halides (Wang et al, 2014), platinum (Liu X. et al, 2016;Wu et al, 2018), cerium oxide (Niu et al, 2007;Celardo et al, 2011), vanadium oxide (André et al, 2011), 2D metallo-porphyrinic metal-organic framework (MOF) nanosheets (Huang et al, 2017), and molybdenum FIGURE 1 | Schematics of cascade reactions for combating infectious biofilms. (A) Different substrates and enzymes involved in substrate transformations to generate different types of ROS.…”

Section: Glucose and Oxygenmentioning

confidence: 99%

Applications and Perspectives of Cascade Reactions in Bacterial Infection Control

Yang

Ren

et al. 2020

Front. Chem.

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Cascade reactions integrate two or more reactions, of which each subsequent reaction can only start when the previous reaction step is completed. Employing natural substrates in the human body such as glucose and oxygen, cascade reactions can generate reactive oxygen species (ROS) to kill tumor cells, but cascade reactions may also have potential as a direly needed, novel bacterial infection-control strategy. ROS can disintegrate the EPS matrix of infectious biofilm, disrupt bacterial cell membranes, and damage intra-cellular DNA. Application of cascade reactions producing ROS as a new infection-control strategy is still in its infancy. The main advantages for infection-control cascade reactions include the fact that they are non-antibiotic based and induction of ROS resistance is unlikely. However, the amount of ROS generated is generally low and antimicrobial efficacies reported are still far <3-4 log units necessary for clinical efficacy. Increasing the amounts of ROS generated by adding more substrate bears the risk of collateral damage to tissue surrounding an infection site. Collateral tissue damage upon increasing substrate concentrations may be prevented by locally increasing substrate concentrations, for instance, using smart nanocarriers. Smart, pH-responsive nanocarriers can self-target and accumulate in infectious biofilms from the blood circulation to confine ROS production inside the biofilm to yield long-term presence of ROS, despite the short lifetime (nanoseconds) of individual ROS molecules. Increasing bacterial killing efficacies using cascade reaction components containing nanocarriers constitutes a first, major challenge in the development of infection-control cascade reactions. Nevertheless, their use in combination with clinical antibiotic treatment may already yield synergistic effects, but this remains to be established for cascade reactions. Furthermore, specific patient groups possessing elevated levels of endogenous substrate (for instance, diabetic or cancer patients) may benefit from the use of cascade reaction components containing nanocarriers.

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Artificial Metalloenzyme‐Based Enzyme Replacement Therapy for the Treatment of Hyperuricemia

Cited by 60 publications

References 64 publications

Enzymosomes: A Rising Effectual Tool for Targeted Drug Delivery System

Enzymosomes: A Rising Effectual Tool for Targeted Drug Delivery System

A Nanozyme‐Based Artificial Peroxisome Ameliorates Hyperuricemia and Ischemic Stroke

Applications and Perspectives of Cascade Reactions in Bacterial Infection Control

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