CeO2@montmorillonite Nanozyme for Crohn’s Disease Therapy

doi:10.7503/cjcu20220476

Abstract

Abstract:

Inflammatory bowel disease（IBD） is a chronic， nonspecific disease that is refractory and therefore affects the normal life of patients to a great extent. Although the global incidence of this disease is increasing year by year， ideal therapeutic drugs are still lacking in clinical practice. Inspired by the antioxidant activity of natural enzymes in organisms， the therapeutic strategies of natural enzymes for inflammatory diseases have come into view. However， natural enzymes have the limitations of poor stability and high cost. Here， we loaded cerium oxide on a montmoril- lonite surface to obtain CeO₂@montmorillonite（CeO₂@MMT） nanozyme and verified that it has an excellent curative effect and universality in the treatment of Crohn’s disease（CD） through in vitro and in vivo experiments. CeO₂@MMT showed good superoxide dismutase- and catalase-like activity in vitro. Its negative charges enable it to target the positively charged intestinal inflammatory site and exert an anti-inflammatory effect at the focus. Thus， it showed obvious curative effects and excellent biosafety in the treatment of CD in mice， which broadened the spectrum of the application of nanozymes.

Key words: Inflammatory bowel disease, Crohn’s disease, Cerium oxide-based nanozyme, Montmorillonite, Reactive oxygen species

CLC Number:

O643

TrendMD:

CHEN Xiwen, CHENG Chaoqun, CHENG Yuan, ZHAO Sheng, WEI Hui. CeO₂@montmorillonite Nanozyme for Crohn’s Disease Therapy[J]. Chem. J. Chinese Universities, 2022, 43(12): 20220476.

Figures/Tables 11

Fig.1 Design and synthesis of CeO2@MMT nanozyme for the treatment of inflammatory bowel disease(IBD)

Fig.2 TEM images of CeO2(A, A′), MMT(B, B′) and CeO2@MMT(C, C′) with different magniflcations

Fig.3 SEM(A—C) and EDS(D—F) images of CeO2(A, D), MMT(B, E), and CeO2@MMT(C, F)

Fig.4 XRD patterns(A), zeta potentials(B) and XPS spectra(C, D) of CeO2,MMT and CeO2@MMT（B） Data are presented as mean±standard error of the mean（n=3）.

Fig.5 ROS scavenging activity of CeO2@MMT（A） CAT-like activity test. Typical kinetic curves of oxygen generation from the decomposition of H2O2 in the presence of indicated materials recorded every 30 s for 10 min. （B） SOD-like activity and •O2‒ scavenging rates of indicated materials. Data are presented as mean±standard error of the mean（n=4）.

Fig.6 Cell viability after incubation with indicated materials for 24 h(A) and ROS level of RAW264.7 macrophages pretreated with indicated materials under H2O2(100 μmol/L) stimulation(B)Data are presented as mean±standard error of the mean（n=5）. ****P < 0.0001 compared to the H2O2 group.

Fig.7 Schematic diagram of the TNBS⁃induced CD model in mice and CeO2@MMT treatment plan

Fig.8 Weight change and colon length statistics of different groups of mice（A） The curves of weight changes of mice in different treatment groups； statistics（B） and photos（C） of colon length of mice in different treatment groups on day 12. Data are presented as mean±standard error of the mean（n=5）. *P < 0.05 compared to the TNBS group.

Fig.9 Colon pathological sections(H&E staining) of different groups of mice on the 11th dayScale bar： 100 μm.

Fig.10 Local concentrations of the proinflammatory cytokines IL⁃1β(A) and TNF⁃α(B) in colon homogenate of different groups of mice on the 12th dayData are presented as mean±standard error of the mean（n = 5）. **** P < 0.0001 and ** P < 0.01， comparison between TNBS group and CeO2@MMT group.

Fig.11 Pathological sections(H&E staining) of the heart, liver, spleen, lung, and kidney of different groups of mice after 7 d(A) and 30 d(B) of administration

References 28

1	Torres J.， Mehandru S.， Colombel J. F.， Peyrin⁃Biroulet L.， Lancet， 2017， 389， 1741―1755
2	Ungaro R.， Mehandru S.， Allen P. B.， Peyrin⁃Biroulet L.， Colombel J. F.， Lancet， 2017， 389， 1756―1770
3	Kaplan G. G.， Nat. Rev. Gastroenterol. Hepatol.， 2015， 12， 720―727
4	Nagao⁃Kitamoto H.， Kitamoto S.， Kamada N.， Cancer Metastasis Rev.， 2022， 1―16
5	Bernstein C. N.， Fried M.， Krabshuis J. H.， Cohen H.， Eliakim R.， Fedail S.， Gearry R.， Goh K. L.， Hamid S.， Khan A. G.， LeMair A. W.， Malfertheiner， Qin O.， Rey J. F.， Sood A.， Steinwurz F.， Thomsen O. O.， Thomson A.， Watermeyer G.， Inflamm. Bowel Dis.， 2010， 16， 112―124
6	Wilson D. S.， Dalmasso G.， Wang L.， Sitaraman S. V.， Merlin D.， Murthy N.， Nat. Mater.， 2010， 9， 923―928
7	Chapkin R. S.， Kamen B. A.， Callaway E. S.， Davidson L. A.， George N. I.， Wang N.， Lupton J. R.， Finnell R. H.， J. Nutr. Biochem.， 2009， 20， 649―655
8	Lautenschlager C.， Schmidt C.， Fischer D.， Stallmach A.， Adv. Drug Deliv. Rev.， 2014， 71， 58―76
9	Farkas S.， Hornung M.， Sattler C.， Anthuber M.， Gunthert U.， Herfarth H.， Schlitt H. J.， Geissler E. K.， Wittig B. M.， Clin. Exp. Immunol.， 2005， 142， 260―267
10	Zhang S.， Ermann J.， Succi M. D.， Zhou A.， Hamilton M. J.， Cao B.， Korzenik J. R.， Glickman J. N.， Vemula P. K.， Glimcher L. H.， Traverso G.， Langer R.， Karp J. M.， Sci. Transl. Med.， 2015， 7， 300ra128
11	Roessner A.， Kuester D.， Malfertheiner P.， Schneider S.， Pathol. Res. Pract.， 2008， 204， 511―524
12	Poli G.， Free Radic. Biol. Med.， 2002， 33， 301―302
13	Zhang Q.， Tao H.， Lin Y.， Hu Y.， An H.， Zhang D.， Feng S.， Hu H.， Wang R.， Li X.， Zhang J.， Biomaterials， 2016， 105， 206―221
14	Wei H.， Wang E.， Chem. Soc. Rev.， 2013， 42， 6060―6093
15	Bao X.， Zhao J.， Sun J.， Hu M.， Yang X.， ACS Nano， 2018， 12， 8882―8892
16	Li S.， Shang L.， Xu B.， Wang S.， Gu K.， Wu Q.， Sun Y.， Zhang Q.， Yang H.， Zhang F.， Gu L.， Zhang T.， Liu H.， Angew. Chem. Int. Ed.， 2019， 58， 12624―12631
17	Li Y.， He X.， Yin J.， Ma Y.， Zhang P.， Li J.， Ding Y.， Zhang J.， Zhao Y.， Chai Z.， Zhang Z.， Angew. Chem. Int. Ed.， 2015， 54， 1832―1835
18	Xi J.， Zhang R.， Wang L.， Xu W.， Liang Q.， Li J.， Jiang J.， Yang Y.， Yan X.， Fan K.， Gao L.， Adv. Funct. Mater.， 2021， 31， 2007130
19	Zhang Y.， Wang F.， Liu C.， Wang Z.， Kang L.， Huang Y.， Dong K.， Ren J.， Qu X.， ACS Nano， 2018， 12， 651―661
20	Zhao S.， Li Y.， Liu Q.， Li S.， Cheng Y.， Cheng C.， Sun Z.， Du Y.， Butch C. J.， Wei H.， Adv. Funct. Mater.， 2020， 30， 2004692―2004706
21	Korsvik C.， Patil S.， Seal S.， Self W. T.， Chem. Commun.（Camb.）， 2007， 10， 1056―1058
22	Reed K.， Cormack A.， Kulkarni A.， Mayton M.， Sayle D.， Klaessig F.， Stadler B.， ChemInform， 2015， 46， 390―405
23	Ivanov V. K.， Shcherbakov A. B.， Usatenko A. V.， Russ. Chem. Rev.， 2009， 78， 855―871
24	Heckert E. G.， Karakoti A. S.， Seal S.， Self W. T.， Biomaterials， 2008， 29， 2705―2709
25	Deshpande S.， Patil S.， Kuchibhatla S. V. N. T.， Seal S.， Appl. Phys. Lett.， 2005， 87， 3113―3115
26	Liu Y.， Cheng Y.， Zhang H.， Zhou M.， Yu Y.， Lin S.， Jiang B.， Zhao X.， Miao L.， Wei C.， Liu Q.， Lin Y.， Du Y.， Butch C. J.， Wei H.， Sci. Adv.， 2020， 6， eabb2695
27	Wirtz S.， Popp V.， Kindermann M.， Gerlach K.， Weigmann B.， Fichtner⁃Feigl S.， Neurath M. F.， Nat. Protoc.， 2017， 12， 1295
28	Neurath M.， Fuss I.， Strober W. Int. Rev. Immunol.， 2000， 19， 51―62

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CeO₂@montmorillonite Nanozyme for Crohn’s Disease Therapy

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