Copper-based Nanozymes: Properties and Applications in Biomedicine

doi:10.15541/jim20220716

Abstract

Abstract:

Natural enzymes play an important role in maintaining normal life activities, but suffer in their inherent instability, harsh reaction conditions and high purification costs, which limit their wide applications in vitro. Compared to natural enzymes, nanozymes with high stability, low cost, and ease of structural regulation and modification attract the great interests and are widely applied to biomedicine, environmental control, industrial production and other fields due to their enzyme-like activities and selectivity. As an essential element and one of the active central metals of natural enzymes in the human body, copper-based (Cu-based) nanozymes have received extensive attentions and researches. This review focused on the classification of Cu-based nanozymes, such as Cu nanozymes, Cu oxide nanozymes, Cu telluride nanozymes, Cu single-atom nanozymes, and Cu-based metal organic framework nanozymes. Then this review described the enzyme-like activities and catalytic mechanisms of Cu-based nanozymes, and also summarized the applications of Cu-based nanozymes, including biosensing, wound healing, acute kidney injury, and tumors. The challenges and future development direction of Cu-based nanozymes were proposed.

Key words: Cu, nanozyme, enzyme-like activity, biomedical application, review

CLC Number:

R318

NIU Jiaxue, SUN Si, LIU Pengfei, ZHANG Xiaodong, MU Xiaoyu. Copper-based Nanozymes: Properties and Applications in Biomedicine[J]. Journal of Inorganic Materials, 2023, 38(5): 489-502.

Figures/Tables 7

Fig. 1 Different types of Cu-based nanozymes[34,56,67⇓⇓-70] (a) TEM image of Cu-Cys NPs[56]; (b) Schematic illustration of CuxO[68]; (c) TEM image of Cu2-xTe[67]; (d~f) Schematic illustration of (d) Cu-TCPP Dots[34], (e) Cu-HCF SSNEs[69] and (f) Cu-N4[70] NPs: Nano particles; Cu-TCPP: Cu-tetrakis(4-carboxyphenyl)porphyrin; Cu-HCF: Cu hexacyanoferrate; SSNEs: Single-site nanozymes

Fig. 2 Antioxidant-like enzyme and ROS scavenging activitivies of Cu-based nanozymes[68,70,86] (a-c) SOD-like (a), GPx-like (b), and POD-like (c) activities of CuxO[68]; (d-f) H2O2 (d), O2·- (e) and free radical (f) scavenging activity of Cu5.4O USNPs[86]; (g) UV-Vis spectra of the reaction solution in the presence of Cu SAs/CN, ascorbic acid and H2O2 over time; (h) Michaelis-Menton curves obtained with different concentrations of substrate AA under the fixed concentration of Cu SAs/CN and H2O2; (i) Quantification for APX-like activities of Cu SAs/CN[70] ROS: Reactive oxigen species; SOD: Superoxide dismutase; SA: Specific activities; AA: Ascorbic acid

Fig. 3 Oxidase-like and ROS generating activity of Cu-based nanozymes[69,81] (a) 1H NMR spectra of GSH at different points during reaction with SSNEs; (b, c) Kinetics of GSHOx-like (b) and POD-like (c) activities of SSNEs and SSNES-G; (d) ·OH generating activity of SSNEs and SSNES-G[69]; (e) 1O2 generating activity of Cu SAzyme with DPBF serving as the indicator; (f) 1O2, O2·- and ·OH generating activity of Cu SAzyme with TEMP, BMPO and DMPO as trapping agents in the presence of H2O2[81] GSH: Glutathione; SSNEs: Single-site nanozyme; GSHOx: Glutathione oxidase; POD: Peroxidase; DPBF: 1,3-diphenyl isobenzofuran; mM: mmol/L; μM: μmol/L

Fig. 4 Cu-based nanozymes for biosensing[94⇓⇓-97] (a) Schematic diagram of a paper sensor for H2O2 detection based on mesoporous CuO hollow sphere nanozymes; (b) Effects of different substrates H2O2, ascorbic acid, Cys, Gly, Pro, Ala, Glu, GSH, Glc, Na+, K+, Ca2+, Mg2+, and Mn2+ on the sensing performance of the paper sensor [94]; (c) UV-Vis spectra of the mixed reaction system with CuO/NiO NTs, TMB, H2O2 and different concentrations of isoniazid; (d) Dose response curve of sensing isoniazid[95]; (e) Schematic illustration of the three-enzyme system (ACC) containing acetylcholinesterase (AchE), choline oxidase (ChOx), and Cu-N-C single atom enzymes (SAzymes) for the organophosphorous pesticide (OP) detection; (f) Change of the absorbance at 652 nm of the ACC system with the addition of OP from 1 to 300 ng/mL; (g) Linear relationship between the inhibition rate (IR) of AchE and the logarithm of OP concentration[96]; (h) Schematic illustration of CuO NPs for ascorbic acid and ALP detection; (i) Emission spectra of different detection systems, with 1-4 indicating AAP-TA-CuO NPs, ALP-TA-CuO NPs, AAP-ALP-TA-CuO NPs, and TA-AA-CuO NPs, respectively; (j) Linear relationship between emission intensity and concentration of ascorbic acid; (k) Calibration plot for ALP determination with different concentrations[97] TMB: 3,3′,5,5′-tetramethylbenzidine; GSH: Glutathione; AChE: Acetylcholinesterase; OP: Organophosphorus pesticide; AAP: L-ascorbate-2-trisodium phosphate; TA: Terephthalic acid; ALP: Alkaline phosphatase; µM: µmol/L; mM: mmol/L

Fig. 5 Cu-based nanozymes for wound healing[86,98] (a) Schematic illustration of the Ni4Cu2 /F127 composite hydrogel dressing in wound healing; (b) Photographs of wounds with different treatments on days 0, 1, 3, 5, and 7 with scale bar representing 5 mm; (c-f) Statistical analysis of the cross-sectional length of wound (c), epidermal thickness (d), granulation tissue thickness (e), number of blood vessels (f) around wound on day 7[98]; (g) Schematic illustration of Cu5.4O USNPs with multiple enzyme-like activities and broad-spectrum ROS scavenging abilities; (h) Photographs of diabetic wounds at different time points with a 6-mm-diameter standard green disc as the size reference; (i) Schematic illustration of Cu5.4O USNPs in diabetic wounds healing; (j) Percentage of wound closure area at different time points; (k) Representative histological images and (l) quantification for the length of regenerated epidermis on day 15 post-surgery; (m) Representative histological images and (n) quantification for the granulation tissue on day 15 post-surgery[86] ROS: Reactive oxigen species; GSH: Glutathione; GSSG: Oxidized glutathione

Fig. 6 Cu-based nanozymes for AKIg[34,86] (a) Schematic illustration of the establishment of AKI and Cu5.4O USNPs for the treatment[86]; (b) Survival curves and the levels of (c) CRE and (d) BUN in different groups at 24 h after treatments[86]; (e, f) The levels of (e) kidney injury molecules-1 (KIM-1) and (f) heme oxygenase-1 (HO-1) in kidney of different groups[86]; (g) Schematic illustration of CTMDs in AKI induced by endotoxemia[34]; (h) Survival curves, (i) levels of oxidative stress containing lactate dehydrogenase (LDH), TNF-α, IL-6, and (j) levels of CREA and BUN[34]; (k) H&E images of different groups[34] PBS: Phosphate buffer solution; AKI: Acute kidney injury; CRE: Creatinine; BUN: Blood urea nitrogen; LPS: Lipopolysaccharide; CTMDs: Cu-tetrakis(4-carboxyphenyl)porphyrin) MOF dots

Fig. 7 Cu-based nanozymes for tumor therapy[56,106] (a) Schematic illustration of Cu-Cys NPs preparation and chemodynamic therapy for tumors; (b, c) Changes in body weight (b) and tumor size (c) of MCF-7R tumor-bearing mice with different treatments; (d) Photographs of tumor in different groups after 40 d of treatment; (e) Average tumor masses excised from MCF-7R tumor-bearing mice from each group[56]; (f) Schematic illustration of the synergistic anticancer mechanism of nHACI based on PDT and PD-1 blockers; (g) Average tumor volume, (h) photographs and (i) weights of tumor in different groups; (j) Survival curves of B16F10 tumor-bearing mice in different groups[106] GSH: Glutathione; GSSG: Oxidized glutathione; ROS: Reactive oxigen species; DOX: Doxorubicin; HHA: Hydrazided hyaluronan

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