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. 2022 Nov 17;12(22):4058.
doi: 10.3390/nano12224058.

Ag-Activated Metal-Organic Framework with Peroxidase-like Activity Synergistic Ag+ Release for Safe Bacterial Eradication and Wound Healing

Jie Zhou  1   2 , Ning Chen  3   4 , Jing Liao  2   3 , Gan Tian  5 , Linqiang Mei  2 , Guoping Yang  1 , Qiang Wang  3 , Wenyan Yin  2
Affiliations

Ag-Activated Metal-Organic Framework with Peroxidase-like Activity Synergistic Ag+ Release for Safe Bacterial Eradication and Wound Healing

Jie Zhou et al. Nanomaterials (Basel). .

Abstract

Silver nanoparticles (Ag NPs), a commonly used antibacterial nanomaterial, exhibit broad-spectrum antibacterial activity to combat drug-resistant bacteria. However, the Ag NPs often causes a low availability and high toxicity to living bodies due to their easy aggregation and uncontrolled release of Ag+ in the bacterial microenvironment. Here, we report a porous metal-organic framework (MOF)-based Zr-2-amin-1,4-NH2-benzenedicarboxylate@Ag (denoted as UiO-66-NH2-Ag) nanocomposite using an in-situ immobilization strategy where Ag NPs were fixed on the UiO-66-NH2 for improving the dispersion and utilization of Ag NPs. As a result, the reduced use dose of Ag NPs largely improves the biosafety of the UiO-66-NH2-Ag. Meanwhile, after activation by the Ag NPs, the UiO-66-NH2-Ag can act as nanozyme with high peroxidase (POD)-like activity to efficiently catalyze the decomposition of H2O2 to extremely toxic hydroxyl radicals (·OH) in the bacterial microenvironment. Simultaneously, the high POD-like activity synergies with the controllable Ag+ release leads to enhanced reactive oxygen species (ROS) generation, facilitating the death of resistant bacteria. This synergistic antibacterial strategy enables the low concentration (12 μg/mL) of UiO-66-NH2-Ag to achieve highly efficient inactivation of ampicillin-resistant Escherichia coli (AmprE. coli) and endospore-forming Bacillus subtilis (B. subtilis). In vivo results illustrate that the UiO-66-NH2-Ag nanozyme has a safe and accelerated bacteria-infected wound healing.

Keywords: antibacterial; metal−organic framework; nanozyme; silver ions release; wound healing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Schematic illustrations of the synthesis process of well-dispersed Ag NPs anchored with porous MOF-based UiO-66-NH2 to form UiO-66-NH2-Ag nanocomposite and their peroxidase-like activity synergistic Ag+ release for high efficient and rapid bacterial elimination.
Figure 1
Figure 1
(a) TEM image of UiO-66-NH2–Ag nanocomposite. (b) XRD patterns of the UiO-66-NH2 and UiO-66-NH2–Ag. (c) Zeta potential of UiO-66-NH2 and UiO-66-NH2-Ag. Data represent mean ± standard error of the mean (n = 3). (d) The high-angle annular dark-field (HAADF)-STEM image of UiO-66-NH2–Ag, and corresponding element mappings of the Ag, O, Zr and N signals. (e) XPS survey plot and (f) Ag 3d spectra of UiO-66-NH2Ag. (g) UV-vis-NIR spectra of UiO-66-NH2 and UiO-66-NH2-Ag aqueous dispersions.
Figure 2
Figure 2
(a) Absorbance spectra of oxTMB in the presence of H2O2 for 10 min using UiO-66-NH2-Ag and UiO-66-NH2. (b) Concentration-dependent POD-like activity of UiO-66-NH2-Ag in the presence of TMB (1 mM) and H2O2 (10 mM). Inset shows the photographs of the reaction system. UiO-66-NH2-Ag concentration rises from left to right. (c) H2O2 concentration-dependent POD-like activity of UiO-66-NH2-Ag. UiO-66-NH2-Ag concentration: 33 μg/mL and TMB concentration: 1 mM. Inset shows the photographs of the reaction system. H2O2 concentration rises from left to right. (d) pH-dependent POD-like activities. Insets from left to right are photos of the reaction system at pH = 2 and pH = 5, respectively. (e) Temperature-dependent POD-like activities. Insets from left to right are photos of the reaction system at different temperature points. Concentrations: TMB (1 mM), H2O2 (10 mM) and UiO-66-NH2-Ag (33 μg/mL). (f) Time-dependent Ag+ release from UiO-66-NH2-Ag at 37 °C with two different pH values.
Figure 3
Figure 3
Photographs of bacterial colonies formed by (a) Ampr E. coli and (b) B. subtilis after exposed to different concentrations of UiO-66-NH2–Ag. (c) Ampr E. coli and (d) B. subtilis killing ratios in (a,b). *** p < 0.001 tested by Student’s t-test.
Figure 4
Figure 4
FE-SEM images of (a) Ampr E. coli and (b) B. subtilis treated with (I) PBS control and different concentrations of (II) 100 μg/mL, (III) 50 μg/mL, (IV) 25 μg/mL, (V) 12 μg/mL, (VI) 6 μg/mL of UiO-66-NH2-Ag. The red arrows show the damaged part.
Figure 5
Figure 5
(a) Schematic diagram of wound healing model establishment and treatment plan. (b) Photographs of Ampr E. coli infected wound treated with PBS, Ag+, UiO-66-NH2-Ag at 0, 3, 6, 8 days. Mouse (c) percent of wound area and (d) body weight during the treatment. (e) Corresponding histological analysis of wound of mice on the 3rd, 6th and 8th day after different treatments. Scale bars: 50 μm. p values were calculated by Student’s t-test: *** p < 0.001.
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References

    1. Wang F., Fang R.H., Luk B.T., Hu C.J., Thamphiwatana S., Dehaini D., Angsantikul P., Kroll A.V., Pang Z., Gao W., et al. Nanoparticle-Based Antivirulence Vaccine for The Management of Methicillin-Resistant Staphylococcus Aureus Skin Infection. Adv. Funct. Mater. 2016;26:1628–1635. doi: 10.1002/adfm.201505231. - DOI - PMC - PubMed
    1. Zhang L., Wang Y., Wang J., Wang Y., Chen A., Wang C., Mo W., Li Y., Yuan Q., Zhang Y. Photon-Responsive Antibacterial Nanoplatform for Synergistic Photothermal-/Pharmaco-Therapy of Skin Infection. ACS Appl. Mater. Interfaces. 2019;11:300–310. doi: 10.1021/acsami.8b18146. - DOI - PubMed
    1. Pan H., Yao X., Chen W., Wang F., He H., Liu L., He Y., Chen J., Jiang P., Zhang R., et al. Dissecting Complicated Viral Spreading of Enterovirus 71 Using in Situ Bioorthogonal Fluorescent Labeling. Biomaterials. 2018;181:199–209. doi: 10.1016/j.biomaterials.2018.07.061. - DOI - PubMed
    1. Whiteley M., Diggle S.P., Greenberg E.P. Progress in and Promise of Bacterial Quorum Sensing Research. Nature. 2017;551:313–320. doi: 10.1038/nature24624. - DOI - PMC - PubMed
    1. Varadi L., Luo J.L., Hibbs D.E., Perry J.D., Anderson R.J., Orenga S., Groundwater P.W. Methods for the Detection and Identification of Pathogenic Bacteria: Past, Present, and Future. Chem. Soc. Rev. 2017;46:4818–4832. doi: 10.1039/C6CS00693K. - DOI - PubMed