Research ArticleHEALTH AND MEDICINE

Integrated cascade nanozyme catalyzes in vivo ROS scavenging for anti-inflammatory therapy

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Science Advances  17 Jul 2020:
Vol. 6, no. 29, eabb2695
DOI: 10.1126/sciadv.abb2695
  • Fig. 1 Schematic illustration of the design of an integrated nanozyme with cascade anti-ROS activity for IBD therapy.

    (A) Cellular cascade enzymes for anti-ROS. The therapeutic efficacy of such a system is limited because of the different subcellular locations of SOD and CAT enzymes and limited extracellular stability. (B) Constructing a cascade nanozyme for anti-ROS therapy by embedding Pt NPs inside PCN222-Mn MOF. Nanoscale proximity of catalytic active sites promotes the cascade reactions. (C) The IBD of mice can be effectively relieved through treatment with the integrated cascade nanozyme.

  • Fig. 2 Synthesis and structural characterization of Pt@PCN222-Mn and related materials.

    (A) Synthesis procedure of Pt@PCN222-Mn. (B) Transmission electron microscopic (TEM) and (C) Scanning electron microscopic (SEM) images of PCN222-Mn. (D) Powder x-ray diffraction (PXRD) patterns of PCN222-Mn, Pt@PCN222-Mn-1, Pt@PCN222-Mn-3, and Pt@PCN222-Mn-5. TEM images of (E) Pt@PCN222-Mn-1, (F) Pt@PCN222-Mn-3, and (G) Pt@PCN222-Mn-5. (H) High-resolution TEM and (I) SEM images of Pt@PCN222-Mn-5. (J) Absorption spectra of PCN222-Mn, Pt@PCN222-Mn-1, Pt@PCN222-Mn-3, and Pt@PCN222-Mn-5. a.u., arbitrary units.

  • Fig. 3 ROS-scavenging activities of Pt@PCN222-Mn and related materials.

    (A) Typical kinetic curves of AA0 (550 nm) for monitoring the reduction of NBT with X and XO in the absence and presence of Pt, PCN222-Mn, Pt@PCN222-Mn-1, Pt@PCN222-Mn-3, and Pt@PCN222-Mn-5. (B) Dependence between the elimination efficiency of O2 and concentrations of nanozymes. (C) Typical kinetic curves of oxygen generation from the decomposition of H2O2 (50 mM) in the presence of Pt, PCN222-Mn, Pt@PCN222-Mn-1, Pt@PCN222-Mn-3, and Pt@PCN222-Mn-5. (D) Dependence between the oxygen-production velocities in the first 60 s and concentrations of nanozymes. The data are shown as means ± SD (n = 3).

  • Fig. 4 Synergistic ROS-scavenging activity of Pt@PCN222-Mn-5.

    (A) Elimination efficiency of O2 with different concentrations of Pt, PCN222-Mn, Pt + PCN222-Mn, and Pt@PCN222-Mn. (B) Oxygen-production velocities in the first 60 s, with different concentrations of Pt, PCN222-Mn, Pt + PCN222-Mn, and Pt@PCN222-Mn. The data are shown as means ± SD (n = 3). ***P < 0.005 and ****P < 0.001; ns, not significant; t test.

  • Fig. 5 UC therapy with Pt@PCN222-Mn-5.

    (A) Overall procedure of the animal experiment (DSS-induced colitis). (B) Daily body-weight development for 10 days. (C) Changes in body weight of mice before (day 7) and after indicated treatments (day 10). (D) Images of the colons and (E) the corresponding colon lengths in indicated groups. (F) IL-1β and (G) TNF-α levels in colon homogenates from indicated groups. (H) H&E-stained colonic sections of mice from indicated groups on day 10. The data are shown as means ± SD (n = 5). *P < 0.05, **P < 0.01, ***P < 0.005, and ****P < 0.001; ns, not significant; t test. Photo credit (D): Yufeng Liu, College of Engineering and Applied Sciences, Nanjing University.

  • Fig. 6 CD therapy with Pt@PCN222-Mn-5.

    (A) Overall procedure of the animal experiment [2,4,6-trinitro benzene sulfonic acid (TNBS)–induced colitis]. (B) Daily body-weight development after administering TNBS solution into the colon lumen. (C) Changes in body weight of mice before (day 9) and after indicated treatments (day 12). (D) Colon lengths and (E) the corresponding images of colons of indicated groups. The data are shown as means ± SD (n = 5). *P < 0.05, ***P < 0.005, and ****P < 0.001; ns, not significant; t test. Photo credit (E): Yuan Cheng, College of Engineering and Applied Sciences, Nanjing University.

Supplementary Materials

  • Supplementary Materials

    Integrated cascade nanozyme catalyzes in vivo ROS scavenging for anti-inflammatory therapy

    Yufeng Liu, Yuan Cheng, He Zhang, Min Zhou, Yijun Yu, Shichao Lin, Bo Jiang, Xiaozhi Zhao, Leiying Miao, Chuan-Wan Wei, Quanyi Liu, Ying-Wu Lin, Yan Du, Christopher J. Butch, Hui Wei

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