A drug-free nanozyme for mitigating oxidative stress and inflammatory bowel disease

Feng Zeng; Yahong Shi; Chunni Wu; Jianming Liang; Qixin Zhong; Karen Briley; Bin Xu; Yongzhuo Huang; Manmei Long; Cong Wang; Jian Chen; Yonghua Tang; Xinying Li; Mengda Jiang; Luting Wang; Qin Xu; Liu Yang; Peng Chen; Shengzhong Duan; Jingyuan Xie; Cong Li; Yingwei Wu

doi:10.1186/s12951-022-01319-7

A drug-free nanozyme for mitigating oxidative stress and inflammatory bowel disease

J Nanobiotechnology. 2022 Mar 4;20(1):107. doi: 10.1186/s12951-022-01319-7.

Authors

Feng Zeng^#¹, Yahong Shi^#², Chunni Wu¹, Jianming Liang¹, Qixin Zhong³, Karen Briley⁴, Bin Xu⁵, Yongzhuo Huang^{6

7

8}, Manmei Long⁹, Cong Wang^{10

11}, Jian Chen¹⁰, Yonghua Tang¹², Xinying Li², Mengda Jiang², Luting Wang⁶, Qin Xu¹, Liu Yang¹³, Peng Chen¹, Shengzhong Duan^{14

15}, Jingyuan Xie¹⁶, Cong Li¹⁷, Yingwei Wu¹⁸

Affiliations

¹ Artemisinin Research Center, Institute of Science and Technology, The First Affiliated Hospital, The First Clinical Medical School, Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510450, China.
² Department of Radiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
³ Department of Cardiovascular, Shenzhen Hospital of Guangzhou University of Chinese Medicine, Shenzhen, 518034, China.
⁴ Invicro, A Konica Minolta Company, Boston, MA, 02210, USA.
⁵ Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200020, China.
⁶ Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
⁷ Zhongshan Institute for Drug Discovery and Development, Chinese Academy of Sciences, Zhongshan, 528437, China.
⁸ School of Advanced Study, Institute of Natural Medicine and Health Product, Taizhou University, Taizhou, 318000, China.
⁹ Department of Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
¹⁰ Key Laboratory of Smart Drug Deliver, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, 201213, China.
¹¹ China Academy for Engineering and Technology, Fudan University, Shanghai, 200433, China.
¹² Radiology Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200020, China.
¹³ Department of Molecular Diagnostics, The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, State Key Laboratory of Medical Genomics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
¹⁴ Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China.
¹⁵ National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, 200011, China.
¹⁶ Department of Nephrology, Institute of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200020, China. nephroxie@163.com.
¹⁷ Key Laboratory of Smart Drug Deliver, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, 201213, China. congli@fudan.edu.cn.
¹⁸ Department of Radiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. wuyw0103@hotmail.com.

^# Contributed equally.

Abstract

Inflammatory bowel disease (IBD) is an incurable disease of the gastrointestinal tract with a lack of effective therapeutic strategies. The proinflammatory microenvironment plays a significant role in both amplifying and sustaining inflammation during IBD progression. Herein, biocompatible drug-free ceria nanoparticles (CeNP-PEG) with regenerable scavenging activities against multiple reactive oxygen species (ROS) were developed. CeNP-PEG exerted therapeutic effect in dextran sulfate sodium (DSS)-induced colitis murine model, evidenced by corrected the disease activity index, restrained colon length shortening, improved intestinal permeability and restored the colonic epithelium disruption. CeNP-PEG ameliorated the proinflammatory microenvironment by persistently scavenging ROS, down-regulating the levels of multiple proinflammatory cytokines, restraining the proinflammatory profile of macrophages and Th1/Th17 response. The underlying mechanism may involve restraining the co-activation of NF-κB and JAK2/STAT3 pathways. In summary, this work demonstrates an effective strategy for IBD treatment by ameliorating the self-perpetuating proinflammatory microenvironment, which offers a new avenue in the treatment of inflammation-related diseases.

Keywords: Ceria nanoparticles; Inflammatory bowel disease; Macrophages; Proinflammatory microenvironment; Reactive oxygen species.

MeSH terms

Animals
Colitis* / drug therapy
Colon / metabolism
Cytokines / metabolism
Dextran Sulfate / adverse effects
Disease Models, Animal
Inflammatory Bowel Diseases* / drug therapy
Mice
Mice, Inbred C57BL
NF-kappa B / metabolism
Oxidative Stress

Substances

Cytokines
NF-kappa B
Dextran Sulfate

Abstract

MeSH terms

Substances

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