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Yang D, Wang R, Zhao L, Xu Y, Zhu Y, Zhang J, Zhou Z, Sun Y, Yang S, Yang H, Wang W. A cerium nanocluster for effective alleviation of inflammatory bowel disease by scavenging RONS and regulating gut microbiome. Mater Today Bio 2025; 32:101705. [PMID: 40230644 PMCID: PMC11995134 DOI: 10.1016/j.mtbio.2025.101705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 03/08/2025] [Accepted: 03/23/2025] [Indexed: 04/16/2025] Open
Abstract
Inflammatory bowel disease (IBD) is characterized by excessive generation of reactive oxygen species and reactive nitrogen species (RONS) within the pro-inflammatory microenvironment. Conventional treatments often have serious side effects, making IBD management challenging. Here, a new cerium cluster, Ce12, with a formula of [Ce12(μ 3-O)8(μ 3-OH)8(μ 2-OH)6(ADA)18]∙3H2O∙3CH3CN (ADA- = 1-adamantanecarboxylate) was prepared and capped with β-cyclodextrin (β-CD) through self-assembly process involving the adamantane moiety of Ce12 and β-CD, resulting in Ce12@CD nanoparticles (NPs). Ce12@CD NPs, with good stability and biocompatibility, exhibit excellent reactive RONS scavenging activities due to the presence of a fraction of Ce3+ ions, offering potential for treating inflammatory diseases. Treatment significantly alleviated body weight loss, colon length reduction, and pathological injury of colon in mice with dextran sodium sulfate (DSS)-elicited colitis, thereby repairing the intestinal mucosal barrier and reducing inflammation. RNA sequence analysis revealed that the therapeutic effects of Ce12@CD NPs are highly correlated with IL-17 and TNF signaling pathways, thereby reducing inflammatory factors such as IL-1β and TNF-α, and alleviating intestinal inflammation. Additionally, Ce12@CD NPs successfully modulated DSS-induced gut microbiota imbalances. This work highlights the unique catalytic activity of Ce12@CD NPs in removing RONS and mimicking biological enzymes, showcasing their potential therapeutic applications for inflammatory disorders.
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Affiliation(s)
- Dan Yang
- Department of Radiology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
- Joint International Research Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, and Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai, 200234, China
| | - Rong Wang
- Joint International Research Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, and Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai, 200234, China
| | - Lei Zhao
- Department of Radiology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Ye Xu
- Institute of Molecular Medicine (IMM), Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Yufeng Zhu
- Joint International Research Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, and Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai, 200234, China
| | - Jingyan Zhang
- Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, 200032, China
| | - Zhiguo Zhou
- Joint International Research Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, and Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai, 200234, China
| | - Yun Sun
- Department of Research and Development, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, 201321, China
| | - Shiping Yang
- Joint International Research Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, and Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai, 200234, China
| | - Hong Yang
- Joint International Research Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, and Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai, 200234, China
| | - Wu Wang
- Department of Radiology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
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Zhang X, Fu X, Chen W, Chen P, Zhu H, Yang B, Liang J, Zeng F. Amelioration of the rheumatoid arthritis microenvironment using celastrol-loaded silver-modified ceria nanoparticles for enhanced treatment. J Nanobiotechnology 2025; 23:372. [PMID: 40405278 PMCID: PMC12100825 DOI: 10.1186/s12951-025-03388-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 04/14/2025] [Indexed: 05/24/2025] Open
Abstract
Rheumatoid arthritis (RA) is characterized by elevated levels of reactive oxygen species (ROS) and a persistent inflammatory microenvironment dominated by M1 macrophages, both of which contribute to disease progression. To address these pathological features, we developed a core-shell nanoplatform consisting of silver-modified ceria nanoparticles loaded with celastrol (Ag-CeNP@Cel). This nanoplatform significantly enhances the water solubility of celastrol and reduces its hepato-renal toxicity by enabling passive accumulation in inflamed joints. The silver-modified ceria nanoparticles synergistically combine with celastrol to scavenge excess ROS and reprogram M1 macrophages into M2 macrophages, thereby mitigating inflammatory responses and improving the rheumatoid arthritis microenvironment (RAM). Ag-CeNP@Cel exhibited robust therapeutic efficacy and safety in preclinical models, presenting an innovative approach to RA treatment by integrating ROS elimination with macrophage modulation to ameliorate inflammatory microenvironment. This study underscores the potential of Ag-CeNP@Cel as a promising therapeutic strategy for RA management.
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Affiliation(s)
- Xiaoru Zhang
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510450, China
| | - Xiaguo Fu
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510450, China
| | - Wanying Chen
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510450, China
| | - Peng Chen
- The First Affiliated Hospital, The First Clinical Medical School, Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510450, China
| | - He Zhu
- The First Affiliated Hospital, The First Clinical Medical School, Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510450, China
| | - Bo Yang
- Zhujiang Hospital, Southern Medical University, No.253 Industrial Avenue, Haizhu District, Guangzhou, 510280, China.
| | - Jianming Liang
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510450, China.
| | - Feng Zeng
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510450, China.
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Wan L, Li S, Du J, Li A, Zhan Y, Zhu W, Zheng P, Qiao D, Nie C, Pan Q. Review of Metal-Polyphenol Self-Assembled Nanoparticles: Synthesis, Properties, and Biological Applications in Inflammatory Diseases. ACS Biomater Sci Eng 2025; 11:2502-2527. [PMID: 40276988 DOI: 10.1021/acsbiomaterials.4c02366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2025]
Abstract
Polyphenols, which are compounds characterized by the presence of phenolic hydroxyl groups, are abundantly found in natural plants and exist in highly complex forms within living organisms. As some of the most prevalent compounds in nature, polyphenols possess significant medicinal value due to their unique structural features, particularly their therapeutic efficacy in antitumor, anti-inflammatory, and antibacterial applications. In the context of inflammation therapy, polyphenolic compounds can inhibit the excessive release of inflammatory mediators from inflammatory cells, thereby mitigating inflammation. Furthermore, these compounds exhibit strong antioxidant properties, enabling them to scavenge free radicals and reactive oxygen species (ROS), reduce oxidative stress-related damage, and exert anti-inflammatory effects. Due to their multiple phenolic hydroxyl groups and their ability to chelate various metals, polyphenols are extensively utilized in the synthesis of self-assembled nanoparticles for the treatment of various diseases. Numerous studies have demonstrated that the therapeutic profile of nanoparticles formed through self-assembly with metal ions surpasses that of polyphenolic compounds alone. This Review will focus on the self-assembly of different polyphenolic compounds with various metal ions to generate nanoparticles, their characterization, and their therapeutic applications in inflammation-related diseases, providing researchers with new insights into the synthetic study of metal-polyphenol nanocomposites and their biological applications.
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Affiliation(s)
- Li Wan
- Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China
| | - Shizhe Li
- Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China
| | - Jiawei Du
- Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China
| | - Anqi Li
- Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China
| | - Yujie Zhan
- Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China
| | - Wufu Zhu
- Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China
| | - Pengwu Zheng
- Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China
| | - Dan Qiao
- Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China
| | - Cunpeng Nie
- Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China
| | - Qingshan Pan
- Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China
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Jiang Y, Chen J, Du Y, Fan M, Shen L. Immune modulation for the patterns of epithelial cell death in inflammatory bowel disease. Int Immunopharmacol 2025; 154:114462. [PMID: 40186907 DOI: 10.1016/j.intimp.2025.114462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 02/23/2025] [Accepted: 03/08/2025] [Indexed: 04/07/2025]
Abstract
Inflammatory bowel disease (IBD) is an inflammatory disease of the intestine whose primary pathological presentation is the destruction of the intestinal epithelium. The intestinal epithelium, located between the lumen and lamina propria, transmits luminal microbial signals to the immune cells in the lamina propria, which also modulate the intestinal epithelium. In IBD patients, intestinal epithelial cells (IECs) die dysfunction and the mucosal barrier is disrupted, leading to the recruitment of immune cells and the release of cytokines. In this review, we describe the structure and functions of the intestinal epithelium and mucosal barrier in the physiological state and under IBD conditions, as well as the patterns of epithelial cell death and how immune cells modulate the intestinal epithelium providing a reference for clinical research and drug development of IBD. In addition, according to the targeting of epithelial apoptosis and necroptotic pathways and the regulation of immune cells, we summarized some new methods for the treatment of IBD, such as necroptosis inhibitors, microbiome regulation, which provide potential ideas for the treatment of IBD. This review also describes the potential for integrating AI-driven approaches into innovation in IBD treatments.
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Affiliation(s)
- Yuting Jiang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Center for Pharmaceutics Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences, Shanghai 201203, China
| | - Jie Chen
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Center for Pharmaceutics Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences, Shanghai 201203, China
| | - Yaoyao Du
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Center for Pharmaceutics Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences, Shanghai 201203, China
| | - Minwei Fan
- State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
| | - Lan Shen
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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Xiong S, Ding X, Zhou L, Liu Z, Jiang W, Ai F, Cai K. An antibacterial and antioxidant rosmarinic acid hydrogel normalizes macrophage polarization to expedite diabetic wound healing. J Colloid Interface Sci 2025; 683:357-371. [PMID: 39736166 DOI: 10.1016/j.jcis.2024.12.138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Revised: 12/17/2024] [Accepted: 12/18/2024] [Indexed: 01/01/2025]
Abstract
The management of diabetic wounds (DW) is a significant challenge within the medical field. Effectively regulating the levels of reactive oxygen species (ROS) at the wound site and orchestrating the inflammatory response are effective strategies for DW treatment. In this study, a novel hydrogel was developed by cross-linking polyboronic acid-modified carboxymethyl chitosan with herbal active ingredient rosmarinic acid (RA), an active herbal ingredient, through dynamic boronic esters formation. In this RA hydrogel (RAgel), RA serves both as an active pharmaceutical ingredient and as a linker for the creation of a dynamic covalent hydrogel, which can decrease the potential toxicity of chemical crosslinking agents and improve the utilization of RA. RAgel demonstrated potential for controlling RA loading and responsiveness to ROS and glucose levels in a diabetic wound environment. Additionally, the intrinsic antioxidant and antibacterial properties of RA were effectively preserved and enhanced upon integration into RAgel. Furthermore, RAgel not only promoted the migration of L929 cells, a key aspect of tissue repair, but also induced M2 polarization in macrophages,while inhibiting the secretion of pro-inflammatory cytokines. In a murine model of diabetic wound healing, RAgel significantly enhanced the proliferation of both the epidermal and granulation tissues. It also exerts a marked anti-inflammatory effect and promotes collagen deposition, thereby expediting the overall wound healing process. The reported RAgel formulation has potential to address the complex challenges associated with diabetic wound management.
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Affiliation(s)
- Shiyu Xiong
- The National Engineering Research Center for Bioengineering Drugs and the Technologies, Jiangxi Provincial Key Laboratory of Bioengineering Drugs, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330038, PR China
| | - Xingwei Ding
- The National Engineering Research Center for Bioengineering Drugs and the Technologies, Jiangxi Provincial Key Laboratory of Bioengineering Drugs, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330038, PR China.
| | - Ling Zhou
- The National Engineering Research Center for Bioengineering Drugs and the Technologies, Jiangxi Provincial Key Laboratory of Bioengineering Drugs, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330038, PR China
| | - Ziqian Liu
- The National Engineering Research Center for Bioengineering Drugs and the Technologies, Jiangxi Provincial Key Laboratory of Bioengineering Drugs, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330038, PR China
| | - Wenyan Jiang
- The National Engineering Research Center for Bioengineering Drugs and the Technologies, Jiangxi Provincial Key Laboratory of Bioengineering Drugs, Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330038, PR China
| | - Fanrong Ai
- School of Advanced Manufacturing, Nanchang University, Nanchang, Jiangxi 330031, PR China.
| | - Kaiyong Cai
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
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殷 丽, 牛 民, 张 可, 耿 志, 胡 建, 李 江, 李 静. [Cimifugin ameliorates Crohn's disease-like colitis in mice by modulating Th-cell immune balance via inhibiting the MAPK pathway]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2025; 45:595-602. [PMID: 40159974 PMCID: PMC11955901 DOI: 10.12122/j.issn.1673-4254.2025.03.17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Indexed: 04/02/2025]
Abstract
OBJECTIVES To investigate the therapeutic effects of cimifugin on Crohn's disease (CD)-like colitis in mice and its possible mechanism. METHODS Thirty adult male C57BL/6 mice were randomized equally into control group, 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced CD-like colitis model group, and cimifugin treatment (daily gavage at 12.5 mg/kg) group. The therapeutic effect of cimifugin was evaluated by observing changes in body weight, disease activity index (DAI) scores, colon length, histopathological inflammation scores, and inflammatory cytokine levels in the colonic mucosa. Intestinal barrier integrity in the mice was assessed using immunofluorescence assay and Western blotting for claudin-1 and ZO-1; T-helper (Th) cell subset ratios in the mesenteric lymph nodes were analyzed with flow cytometry. Network pharmacology, KEGG enrichment analysis and molecular docking were used to predict the targets of cimifugin and analyze the key pathways and cimifugin-MAPK protein interactions, which were validated by Western blotting in the mouse models. RESULTS In mice with TNBS-induced colitis, cimifugin treatment significantly attenuated body weight loss and colon shortening, lowered DAI and histopathological scores, decreased IFN-γ and IL-17 levels, and increased IL-4 and IL-10 levels in the colonic mucosa. Cimifugin treatment also significantly improved TNBS-induced claudin-1 dislocation and reduction of goblet cells, upregulated claudin-1 and ZO-1 expressions, reduced Th1 and Th17 cell percentages, and increased Th2 and Treg cell percentages in the colonic mucosa of the mice. KEGG analysis suggested a possible connection between the effect of cimifugin and MAPK signaling, and molecular docking showed strong binding affinity between cimifugin and MAPK core proteins. Western blotting demonstrated significantly decreased phosphorylation levels of JNK, ERK, and p38 in the colonic mucosa of cimifugin-treated mouse models. CONCLUSIONS Cimifugin alleviates TNBS-induced CD-like colitis by repairing intestinal barrier damage and restoring Th1/Th2 and Th17/Treg balance via suppressing MAPK pathway activation.
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Rana SVS. Mechanistic paradigms of immunotoxicity, triggered by nanoparticles - a review. Toxicol Mech Methods 2025; 35:262-278. [PMID: 39585654 DOI: 10.1080/15376516.2024.2431687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 11/04/2024] [Accepted: 11/14/2024] [Indexed: 11/26/2024]
Abstract
Nanoparticles (NPs) possess the ability to penetrate cells and elicit a rapid and targeted immune response, influenced by their distinct physicochemical properties. These particles can engage with both micro and macromolecules, thereby impacting various downstream signaling pathways that may lead to cell death. This review provides a comprehensive overview of the primary mechanisms contributing to the immunotoxicity of both organic and inorganic nanoparticles. The effects of carbon-based nanomaterials (CNMs), including single-walled carbon nanotubes, multi-walled carbon nanotubes, graphene, and metal oxide nanoparticles, on various immune cell types such as macrophages, neutrophils, monocytes, dendritic cells (DCs), antigen-presenting cells (APCs), and RAW 264.7 cells are examined. The immune responses discussed encompass inflammation, oxidative stress, autophagy, and apoptosis. Additionally, the roles of pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α, and IFN-γ, along with JAK/STAT signaling pathways, are highlighted. The interaction of NPs with oxidative stress pathways, including MAPK signaling and Nrf2/ARE signaling, is also explored. Furthermore, the mechanisms by which nanoparticles induce damage to organelles such as lysosomes, the endoplasmic reticulum, exosomes, and Golgi bodies within the immune system are addressed. The review also emphasizes the genotoxic and epigenetic mechanisms associated with the immunotoxicity of NPs. Recent advancements regarding the immunotherapeutic potential of engineered NPs are reported. The roles of autophagy and apoptosis in the immunotoxicity of NPs merit further investigation. In conclusion, understanding how engineered nanoparticles modulate immune responses may facilitate the prevention and treatment of human diseases, including cancer and autoimmune disorders.
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Affiliation(s)
- S V S Rana
- Department of Toxicology, Chaudhary Charan Singh University, Meerut, India
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Mi L, Zhang K, Ma JX, Yao JF, Tong YL, Bao ZJ. Hollow cerium nanoparticles synthesized by one-step method for multienzyme activity to reduce colitis in mice. World J Gastroenterol 2025; 31:98732. [PMID: 39926211 PMCID: PMC11718602 DOI: 10.3748/wjg.v31.i5.98732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 10/08/2024] [Accepted: 12/04/2024] [Indexed: 12/30/2024] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a common chronic intestinal inflammatory disease. High oxidative stress is a treatment target for IBD. Cerium oxide (CeO2) nanomaterials as nanozymes with antioxidant activity are potential drugs for the treatment of colitis. AIM To synthesize hollow cerium (H-CeO2) nanoparticles by one-step method and to validate the therapeutic efficacy of H-CeO2 in IBD. METHODS H-CeO2 was synthesized by one-step method and examined its characterization and nanoenzymatic activity. Subsequently, we constructed dextran sulfate sodium (DSS)-induced colitis in mice to observe the effects of H-CeO2 on colonic inflammation. The effects of H-CeO2 on colon inflammation and reactive oxygen species (ROS) levels in IBD mice were detected by hematoxylin and eosin staining and dichlorofluorescein diacetate staining, respectively. Finally, the biological safety of H-CeO2 on mice was evaluated by hematoxylin and eosin staining, blood routine, and blood biochemistry. RESULTS H-CeO2 nanoparticles prepared by the one-step method were uniform, monodisperse and hollow. H-CeO2 had a good ability to scavenge ROS, ∙OH and ∙OOH. H-CeO2 reduced DSS-induced decreases in body weight and colon length, colonic epithelial damage, inflammatory infiltration, and ROS accumulation. H-CeO2 administration reduced the disease activity index of DSS-induced animals from about 8 to 5. H-CeO2 had no significant effect on body weight, total platelet count, hemoglobin, white blood cell, and red blood cell counts in healthy mice. No significant damage to major organs was observed in healthy mice following H-CeO2 administration. CONCLUSION The one-step synthesis of H-CeO2 nanomaterials had good antioxidant activity, biosafety, and inhibited development of DSS-induced IBD in mice by scavenging ROS.
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Affiliation(s)
- Lin Mi
- Department of General Medicine, Huadong Hospital, Fudan University, Shanghai 200040, China
| | - Kai Zhang
- Department of General Medicine, Huadong Hospital, Fudan University, Shanghai 200040, China
| | - Jian-Xia Ma
- Department of Gastroenterology, Huadong Hospital, Fudan University, Shanghai 200040, China
| | - Jian-Feng Yao
- Department of Gastroenterology, Huadong Hospital, Fudan University, Shanghai 200040, China
| | - Yi-Li Tong
- Department of General Medicine, Huadong Hospital, Fudan University, Shanghai 200040, China
| | - Zhi-Jun Bao
- Department of Gastroenterology, Huadong Hospital, Fudan University, Shanghai 200040, China
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Wang H, Zhou F, Shen M, Ma R, Yu Q. Classification of Nanomaterial Drug Delivery Systems for Inflammatory Bowel Disease. Int J Nanomedicine 2025; 20:1383-1399. [PMID: 39925683 PMCID: PMC11804237 DOI: 10.2147/ijn.s502546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 01/16/2025] [Indexed: 02/11/2025] Open
Abstract
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, primarily arises from defects in the colonic barrier, imbalances of the gut microbiota, and immune response issues. These complex causes make it difficult to achieve a complete cure. Patients with IBD frequently experience recurrent abdominal pain and bloody diarrhea, while severe cases may result in intestinal obstruction, perforation, and cancer. Lifelong maintenance therapy may thus be needed to manage these symptoms; however, traditional IBD drugs, such as 5-aminosalicylic acid, glucocorticoids, immunosuppressants, and biological agents, are often associated with problems including poor solubility, instability, and ineffective targeting, as well as causing serious side effects in non-target tissues. Nanomaterial drug delivery systems (NDDS) have recently shown great promise in optimizing drug distribution, solubility through biocompatible coatings, enhancing bioavailability via PEGylation and reducing side effects. These formulations can enhance a drug's pharmacokinetics by modifying its properties, improve its ability to cross barriers, and boost bioavailability. In addition, NDDS can enable targeted delivery, increase local drug concentrations, improve efficacy, and reduce side effects, as well as protecting active drug molecules from immune recognition and protease degradation. The clinical use of these systems for treating IBD, however, requires further research. This review summarizes the classification of NDDS for IBD, and concludes that, despite ongoing challenges, NDDS may represent an effective treatment approach for IBD. In summary, NDDS enhance the targeted delivery of therapeutic agents to specific cells or tissues, thereby improving drug bioavailability and therapeutic efficacy. These systems effectively surmount biological barriers, facilitating efficient drug delivery to targeted sites, which is crucial for attaining optimal therapeutic outcomes. This review contributes to a deeper understanding of how the physicochemical properties of NDDS influence pharmacological behavior in vivo and can expedite their clinical translation.
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Affiliation(s)
- Haichen Wang
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, 215002, People’s Republic of China
| | - Feifei Zhou
- Department of Gastroenterology, Suzhou City Wuzhong District Chengnan Street Community Health Service Center, Suzhou, Jiangsu, 215002, People’s Republic of China
| | - Mengdan Shen
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, 215002, People’s Republic of China
| | - Ronglin Ma
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, 215002, People’s Republic of China
| | - Qiang Yu
- Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, 215002, People’s Republic of China
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Rezaie N, Aghamohammad S, Khiavi EHAG, Talebi M, Pourshafie MR, Rohani M. The Analysis and Comparison of Anti-Inflammatory and Antioxidant Characteristics of Postbiotic and Paraprobiotic Derived From Novel Native Probiotic Cocktail in DSS-Induced Colitic Mice. Food Sci Nutr 2025; 13:e70034. [PMID: 39931269 PMCID: PMC11808210 DOI: 10.1002/fsn3.70034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 01/06/2025] [Accepted: 01/21/2025] [Indexed: 02/13/2025] Open
Abstract
Oxidative stress, particularly when precipitated by the intake of a diet rich in fats, has the potential to induce an inflammatory state. Therefore, it is crucial to consider the administration of agents possessing antioxidant and anti-inflammatory properties for the benefit of these patients. The objective of this study was to investigate the ability of postbiotic and paraprobiotic substances to regulate oxidative stress and inflammation. We hypothesized that both postbiotics and paraprobiotics could demonstrated significant efficacy in reducing oxidative stress and inflammation, with distinct differences in their effectiveness. A total of 88 Lactobacillus and Bifidobacterium strains were assessed for antioxidant activity. Male C57BL/6 mice were divided into four groups: HFD + PBS, HFD + DSS, HFD + DSS + postbiotic, and HFD + DSS + paraprobiotic. Various parameters, including weight change, disease activity index, and gene expression analysis, as well as enzymes involved in oxidative activities and inflammation were evaluated after treatment with derivatives of six selected strains. In comparison with the groups exposed to DSS, mice treated with a combination of postbiotic and paraprobiotic alongside DSS exhibited a reduction in DSS-induced negative effects on both phenotypical characteristics and molecular indices, particularly the Nrf2- and NF-kB-related genes, with a notable focus on postbiotic. Based on the results, it can be inferred that despite the utilization of an unhealthy regime that may worsen oxidative stress and inflammation, the condition can be efficiently controlled by employing secure variations of probiotics, such as paraprobiotic and postbiotic components, with a particular emphasis on postbiotics.
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Affiliation(s)
- Niloofar Rezaie
- Department of BacteriologyPasteur Institute of IranTehranIran
| | | | | | - Malihe Talebi
- Department of Microbiology, School of MedicineIran University of Medical SciencesTehranIran
| | | | - Mahdi Rohani
- Department of BacteriologyPasteur Institute of IranTehranIran
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Chen J, Yin C, Zhang Y, Lai X, Liu C, Luo Y, Luo J, He J, Yu B, Wang Q, Wang H, Chen D, Wu A. EGCG Alleviates DSS-Induced Colitis by Inhibiting Ferroptosis Through the Activation of the Nrf2-GPX4 Pathway and Enhancing Iron Metabolism. Nutrients 2025; 17:547. [PMID: 39940407 PMCID: PMC11820173 DOI: 10.3390/nu17030547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2024] [Revised: 01/10/2025] [Accepted: 01/26/2025] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND Ferroptosis is a regulated cell death process linked to various diseases. This study explored whether Epigallocatechin-3-gallate (EGCG), a tea-derived antioxidant, could regulate ferroptosis to alleviate dextran sulfate sodium (DSS)-induced colitis. METHODS A DSS-induced colitis model was used to assess EGCG's effects. Ferroptosis markers, oxidative stress, and iron metabolism were evaluated, alongside Nrf2-GPX4 pathway activation and ferritin (FTH/L) expression. RESULTS Iron dysregulation and oxidative stress contributed to DSS-induced colitis by activating ferroptosis in colonic epithelial cells. EGCG supplementation inhibited ferroptosis, reducing oxidative damage. Mechanistically, EGCG activated the Nrf2-GPX4 pathway, enhancing antioxidant defense, and improved iron metabolism by upregulating ferritin expression. CONCLUSIONS EGCG effectively suppressed DSS-induced ferroptosis and colitis, highlighting its potential as a ferroptosis inhibitor and therapeutic agent.
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Affiliation(s)
- Junzhou Chen
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.C.); (C.Y.); (Y.Z.); (X.L.); (C.L.); (Y.L.); (J.L.); (J.H.); (B.Y.); (Q.W.); (H.W.)
- Key Laboratory for Animal Disease-Resistance Nutrition, China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Conghui Yin
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.C.); (C.Y.); (Y.Z.); (X.L.); (C.L.); (Y.L.); (J.L.); (J.H.); (B.Y.); (Q.W.); (H.W.)
- Key Laboratory for Animal Disease-Resistance Nutrition, China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Yilong Zhang
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.C.); (C.Y.); (Y.Z.); (X.L.); (C.L.); (Y.L.); (J.L.); (J.H.); (B.Y.); (Q.W.); (H.W.)
- Key Laboratory for Animal Disease-Resistance Nutrition, China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Xin Lai
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.C.); (C.Y.); (Y.Z.); (X.L.); (C.L.); (Y.L.); (J.L.); (J.H.); (B.Y.); (Q.W.); (H.W.)
- Key Laboratory for Animal Disease-Resistance Nutrition, China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Chen Liu
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.C.); (C.Y.); (Y.Z.); (X.L.); (C.L.); (Y.L.); (J.L.); (J.H.); (B.Y.); (Q.W.); (H.W.)
- Key Laboratory for Animal Disease-Resistance Nutrition, China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Yuheng Luo
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.C.); (C.Y.); (Y.Z.); (X.L.); (C.L.); (Y.L.); (J.L.); (J.H.); (B.Y.); (Q.W.); (H.W.)
- Key Laboratory for Animal Disease-Resistance Nutrition, China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Junqiu Luo
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.C.); (C.Y.); (Y.Z.); (X.L.); (C.L.); (Y.L.); (J.L.); (J.H.); (B.Y.); (Q.W.); (H.W.)
- Key Laboratory for Animal Disease-Resistance Nutrition, China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Jun He
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.C.); (C.Y.); (Y.Z.); (X.L.); (C.L.); (Y.L.); (J.L.); (J.H.); (B.Y.); (Q.W.); (H.W.)
- Key Laboratory for Animal Disease-Resistance Nutrition, China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Bing Yu
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.C.); (C.Y.); (Y.Z.); (X.L.); (C.L.); (Y.L.); (J.L.); (J.H.); (B.Y.); (Q.W.); (H.W.)
- Key Laboratory for Animal Disease-Resistance Nutrition, China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Quyuan Wang
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.C.); (C.Y.); (Y.Z.); (X.L.); (C.L.); (Y.L.); (J.L.); (J.H.); (B.Y.); (Q.W.); (H.W.)
- Key Laboratory for Animal Disease-Resistance Nutrition, China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Huifen Wang
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.C.); (C.Y.); (Y.Z.); (X.L.); (C.L.); (Y.L.); (J.L.); (J.H.); (B.Y.); (Q.W.); (H.W.)
- Key Laboratory for Animal Disease-Resistance Nutrition, China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Daiwen Chen
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.C.); (C.Y.); (Y.Z.); (X.L.); (C.L.); (Y.L.); (J.L.); (J.H.); (B.Y.); (Q.W.); (H.W.)
- Key Laboratory for Animal Disease-Resistance Nutrition, China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
| | - Aimin Wu
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China; (J.C.); (C.Y.); (Y.Z.); (X.L.); (C.L.); (Y.L.); (J.L.); (J.H.); (B.Y.); (Q.W.); (H.W.)
- Key Laboratory for Animal Disease-Resistance Nutrition, China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, China
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Gong Z, Chen Z, Li D, Lu X, Wu J, Sun H, Wang X, Liu S, Xia X, Lu F, Jiang J, Sun C, Wang H, Zeng F, Ma X. Hydrogel loaded with cerium-manganese nanoparticles and nerve growth factor enhances spinal cord injury repair by modulating immune microenvironment and promoting neuronal regeneration. J Nanobiotechnology 2025; 23:29. [PMID: 39833803 PMCID: PMC11748312 DOI: 10.1186/s12951-025-03098-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Accepted: 01/07/2025] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Spinal cord injury (SCI) treatment remains a formidable challenge, as current therapeutic approaches provide only marginal relief and fail to reverse the underlying tissue damage. This study aims to develop a novel composite material combining enzymatic nanoparticles and nerve growth factor (NGF) to modulate the immune microenvironment and enhance SCI repair. METHODS CeMn nanoparticles (NP) and CeMn NP-polyethylene glycol (PEG) nanozymes were synthesized via sol-gel reaction and DSPE-mPEG modification. Transmission Electron Microscopy, Selected-Area Electron Diffraction, X-ray Diffraction and X-ray Photoelectron Spectroscopy confirmed their crystalline structure, mixed-valence states, and redox properties. Size uniformity, biocompatibility, and catalytic activity were assessed via hydrodynamic diameter, zeta potential, and elemental analysis. The Lightgel/NGF/CeMn NP-PEG composite was synthesized and characterized via electron microscopy, compression testing, rheological analysis, NGF release kinetics, and 30-day degradation studies. Both in vitro and in vivo experiments were conducted to evaluate the therapeutic effects of the composite on SCI. RESULTS The Lightgel/NGF/CeMn NP-PEG composite was successfully synthesized, exhibiting favorable physical properties. At a CeMn NP-PEG concentration of 4 µg/mL, the composite maintained cell viability and demonstrated enhanced biological activity. It also showed superior mechanical properties and an effective NGF release profile. Notably, the composite significantly upregulated the expression of nerve growth-associated proteins, reduced inflammatory cytokines, scavenged reactive oxygen species (ROS), and promoted M2 macrophage polarization by inhibiting the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. In a rat SCI model, it facilitated functional recovery and attenuated inflammation. CONCLUSION The Lightgel/NGF/CeMn NP-PEG composite shows significant therapeutic promise for SCI, effectively eliminating ROS, promoting M2 macrophage polarization, reducing pro-inflammatory cytokines, and supporting neuronal regeneration. These effects substantially enhance motor function in SCI rats, positioning it as a promising candidate for future clinical applications.
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Affiliation(s)
- Zhaoyang Gong
- Department of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China
| | - Zhenhao Chen
- Department of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China
| | - Dachuan Li
- Department of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China
| | - Xiao Lu
- Department of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China
| | - Jianwei Wu
- Department of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China
| | - Hanqiu Sun
- Department of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China
| | - Ximeng Wang
- Department of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China
| | - Siyang Liu
- Department of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China
| | - Xinlei Xia
- Department of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China
| | - Feizhou Lu
- Department of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China
| | - Jianyuan Jiang
- Department of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China
| | - Chi Sun
- Department of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China.
| | - Hongli Wang
- Department of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China.
| | - Feng Zeng
- 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.
| | - Xiaosheng Ma
- Department of Orthopedics, Huashan Hospital, Fudan University, No. 12, Middle Wulumuqi Road, Jing'an District, Shanghai, 200040, China.
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Wu J, Chen Z, Huang H, Wang H, Wang X, Lu Z, Xu H, Ma X, Zeng F, Wang H. Custom-Made Ce-Mn Bimetallic Nanozyme for the Treatment of Intervertebral Disc Degeneration by Inhibiting Oxidative Stress and Modulating Macrophage M1/M2 Polarization. Biomater Res 2024; 28:0118. [PMID: 39717477 PMCID: PMC11665849 DOI: 10.34133/bmr.0118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 11/04/2024] [Accepted: 11/12/2024] [Indexed: 12/25/2024] Open
Abstract
Intervertebral disc degeneration (IDD)-induced lower back pain (LBP) brings heavy burden worldwide. In the degenerated intervertebral disc, there is an increase in the accumulation of reactive oxygen species (ROS) and the infiltration of M1 macrophages, which leads to abnormal local inflammatory microenvironment and exacerbates IDD. In this study, we developed a novel injectable polyethylene glycol (PEG)-capped cerium ion-manganese ion (Ce-Mn) bimetallic nanozyme (CeMn-PEG) with strong ROS scavenging and M2-type macrophage polarizing abilities to efficiently alleviate IDD. In vitro experiments demonstrated that CeMn-PEG effectively scavenged excess ROS in both nucleus pulposus (NP) and RAW264.7 cells. In addition, we found that CeMn-PEG markedly protected NP cells from H2O2-induced overproduction of inflammatory cytokines, excessive cell apoptosis and autophagy, and imbalance between extracellular matrix (ECM) degradation. Moreover, CeMn-PEG induced macrophages to transition from the M1 phenotype to the M2 phenotype and the increased M2-type macrophages could alleviate H2O2-induced ECM degradation and cell apoptosis in NP cells. In a puncture-induced mouse IDD model, CeMn-PEG treatment could effectively ameliorate the progression of disc degeneration and mitigate puncture-induced mechanical hyperalgesia. Thus, our study demonstrated the effectiveness of CeMn-PEG as a novel treatment strategy for the treatment of IDD and a range of other inflammatory diseases.
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Affiliation(s)
- Jianwei Wu
- Department of Orthopedics, Huashan Hospital,
Fudan University, Shanghai 200000, China
| | - Zhenhao Chen
- Department of Orthopedics, Huashan Hospital,
Fudan University, Shanghai 200000, China
| | - Han Huang
- Department of Orthopedics, Huashan Hospital,
Fudan University, Shanghai 200000, China
| | - Hongwei Wang
- Department of Orthopedics, Huashan Hospital,
Fudan University, Shanghai 200000, China
| | - Xianghe Wang
- Department of Orthopedics, Huashan Hospital,
Fudan University, Shanghai 200000, China
| | - Zian Lu
- Department of Orthopedics, Huashan Hospital,
Fudan University, Shanghai 200000, China
| | - Haocheng Xu
- Department of Orthopedics, Huashan Hospital,
Fudan University, Shanghai 200000, China
| | - Xiaosheng Ma
- Department of Orthopedics, Huashan Hospital,
Fudan University, Shanghai 200000, China
| | - Feng Zeng
- Artemisinin Research Center,
Guangzhou University of Chinese Medicine, Guangzhou 510450, China
| | - Hongli Wang
- Department of Orthopedics, Huashan Hospital,
Fudan University, Shanghai 200000, China
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Yang L, Hu M, Shao J. Integration of Gut Mycobiota and Oxidative Stress to Decipher the Roles of C-Type Lectin Receptors in Inflammatory Bowel Diseases. Immunol Invest 2024; 53:1177-1204. [PMID: 39115960 DOI: 10.1080/08820139.2024.2388164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/10/2024]
Abstract
BACKGROUND Ulcerative colitis (UC) and Crohn's disease (CD) are two subtypes of inflammatory bowel disease (IBD) with rapidly increased incidence worldwide. Although multiple factors contribute to the occurrence and progression of IBD, the role of intestinal fungal species (gut mycobiota) in regulating the severity of these conditions has been increasingly recognized. C-type lectin receptors (CLRs) on hematopoietic cells, including Dectin-1, Dectin-2, Dectin-3, Mincle and DC-SIGN, are a group of pattern recognition receptors (PRRs) that primarily recognize fungi and mediate defense responses, such as oxidative stress. Recent studies have demonstrated the indispensable role of CLRs in protecting the colon from intestinal inflammation and mucosal damage. METHODS AND RESULTS This review provides a comprehensive overview of the role of CLRs in the pathogenesis of IBD. Given the significant impact of mycobiota and oxidative stress in IBD, this review also discusses recent advancements in understanding how these factors exacerbate or ameliorate IBD. Furthermore, the latest developments in CLR-guided IBD therapy are examined to highlight the modulation of CLRs in fungal recognition and oxidative burst during the IBD process. CONCLUSION This review emphasizes the importance of CLRs in IBD, offering new perspectives on the etiology and therapeutic approaches for this disease.
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Affiliation(s)
- Liu Yang
- Laboratory of Anti-infection and Immunity, College of Integrated Chinese and Western Medicine (College of Life Science), Anhui University of Chinese Medicine, Hefei, Anhui 230012, P. R. China
| | - Min Hu
- Department of pathology, College of Integrated Chinese and Western Medicine (College of Life Science), Anhui University of Chinese Medicine, Hefei, Anhui, P. R. China
| | - Jing Shao
- Laboratory of Anti-infection and Immunity, College of Integrated Chinese and Western Medicine (College of Life Science), Anhui University of Chinese Medicine, Hefei, Anhui 230012, P. R. China
- Institute of Integrated Traditional Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, Anhui, P. R. China
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15
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Summer M, Ashraf R, Ali S, Bach H, Noor S, Noor Q, Riaz S, Khan RRM. Inflammatory response of nanoparticles: Mechanisms, consequences, and strategies for mitigation. CHEMOSPHERE 2024; 363:142826. [PMID: 39002651 DOI: 10.1016/j.chemosphere.2024.142826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Revised: 07/08/2024] [Accepted: 07/09/2024] [Indexed: 07/15/2024]
Abstract
Numerous nano-dimensioned materials have been generated as a result of several advancements in nanoscale science such as metallic nanoparticles (mNPs) which have aided in the advancement of related research. As a result, several significant nanoscale materials are being produced commercially. It is expected that in the future, products that are nanoscale, like mNPs, will be useful in daily life. Despite certain benefits, widespread use of metallic nanoparticles and nanotechnology has negative effects and puts human health at risk because of their continual accumulation in closed biological systems, along with their complex and diverse migratory and transformation pathways. Once within the human body, nanoparticles (NPs) disrupt the body's natural biological processes and trigger inflammatory responses. These NPs can also affect the immune system by activating separate pathways that either function independently or interact with one another. Cytotoxic effects, inflammatory response, genetic material damage, and mitochondrial dysfunction are among the consequences of mNPs. Oxidative stress and reactive oxygen species (ROS) generation caused by mNPs depend upon a multitude of factors that allow NPs to get inside cells and interact with biological macromolecules and cell organelles. This review focuses on how mNPs cause inflammation and oxidative stress, as well as disrupt cellular signaling pathways that support these effects. In addition, possibilities and problems to be reduced are addressed to improve future research on the creation of safer and more environmentally friendly metal-based nanoparticles for commercial acceptance and sustainable use in medicine and drug delivery.
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Affiliation(s)
- Muhammad Summer
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan.
| | - Rimsha Ashraf
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Shaukat Ali
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Horacio Bach
- Department of Medicine, Division of Infectious Diseases, 2660 Oak Street, Vancouver, BC, V6H3Z6, Canada
| | - Shehzeen Noor
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Qudsia Noor
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Saima Riaz
- Medical Toxicology and Biochemistry Laboratory, Department of Zoology, Government College University, Lahore, 54000, Pakistan
| | - Rana Rashad Mahmood Khan
- Department of Chemistry, Government College University Lahore, Faculty of Chemistry and Life Sciences, Pakistan
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He Y, Shen X, Peng H. Effects and Mechanisms of the Xianhecao-Huanglian Drug Pair on Autophagy-Mediated Intervention in Acute Inflammatory Bowel Disease via the JAK2/STAT3 Pathway. Biol Proced Online 2024; 26:27. [PMID: 39187810 PMCID: PMC11346250 DOI: 10.1186/s12575-024-00242-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 05/09/2024] [Indexed: 08/28/2024] Open
Abstract
To explore the effects and mechanisms of the Xianhecao-Huanglian drug pair on autophagy-mediated intervention in acute inflammatory bowel disease (IBD) via the JAK2/STAT3 pathway. The study examined the underlying mechanisms of action of Xianhecao (APL) and Huanglian (CR) using a mouse model of dextran sodium sulfate (DSS)-induced acute inflammatory bowel disease (IBD) and in an in vitro model of IBD induced by lipopolysaccharide (LPS). The assessment of the therapeutic efficacy of the Xianhecao-Huanglian drug combination in a mouse model of IBD caused by DSS included the following parameters: Assessment of weight loss or gain. Measurement of the disease activity index (DAI). Assessment of histological damage. Determination of organ index. Measurement of colon length. Ascertain the levels of inflammatory cytokines in the intestinal tissues and serum of mice. Immunohistochemistry (IHC) for the measurement of tight junction protein concentrations in the colon mucosa, including ZO-1, claudin-1, and occludin. Measurement of mucin levels, specifically Mucin 2 (Muc2). Hematoxylin and eosin (HE) staining for the observation of histopathological alterations in colonic tissues. Examining the effect on goblet cells using periodic acid-Schiff (PAS) labeling. Application of Western blot and immunofluorescence techniques for the detection of autophagy-related markers in colonic tissues and proteins associated with the JAK2/STAT3 pathway. A cell inflammation model of IBD was induced through LPS stimulation, and a serum containing the Xianhecao-Huanglian drug pair (referred to as ACHP-DS) was formulated. Cell viability, anti-proinflammatory cytokines, tight junction proteins, mucins, autophagy-related markers, and the JAK2/STAT3 signaling pathway were assessed. The Xianhecao-Huanglian drug pair significantly ameliorated the symptoms and survival quality of acute IBD mice, reducing the disease activity index score, raising MUC2 secretion and tight junction protein expression to improve the integrity of the intestinal barrier, and preserving goblet cell function; thus, protecting the intestines. It effectively restrained triggering the signaling pathway that involves JAK2 and STAT3, leading to the suppression of inflammation and amelioration of colonic inflammation damage. Additionally, it induced autophagy in mouse colonic tissues.The in vitro experiments demonstrated that the Xianhecao-Huanglian drug combination enhanced the viability of LOVO and NCM460 cells when exposed to LPS stimulation. Furthermore, it suppressed the production of inflammatory cytokines such as IL-6, IL-1β, as well as TNF-α, whilst increasing the production of IL-10, ZO-1, along with MUC2. These effects collectively led to the alleviation of inflammation and the restoration of mucosal integrity. The results were consistent with what was shown in the in vivo trial. Moreover, the medication demonstrated effectiveness in reducing JAK2 along with STAT3 phosphorylation levels in the LPS-induced inflammatory model of IBD cells. The intervention with either the Xianhecao-Huanglian drug combination-containing serum or the JAK2/STAT3 pathway inhibitor AG490 reversed the pro-inflammatory effects and increased autophagy levels in the LPS-stimulated cells. The Xianhecao-Huanglian drug combination modulates the JAK2/STAT3 pathway, leading to the induction of autophagy, which serves as an intervention for IBD.
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Affiliation(s)
- Yaping He
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China.
| | - Xinling Shen
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
| | - Haiyan Peng
- The First Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu, China.
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Tang B, Xie X, Lu J, Huang W, Yang J, Tian J, Lei L. Designing biomaterials for the treatment of autoimmune diseases. APPLIED MATERIALS TODAY 2024; 39:102278. [DOI: 10.1016/j.apmt.2024.102278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/04/2024]
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18
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Wang Y, He X, Huang K, Cheng N. Nanozyme as a rising star for metabolic disease management. J Nanobiotechnology 2024; 22:226. [PMID: 38711066 PMCID: PMC11071342 DOI: 10.1186/s12951-024-02478-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 04/15/2024] [Indexed: 05/08/2024] Open
Abstract
Nanozyme, characterized by outstanding and inherent enzyme-mimicking properties, have emerged as highly promising alternatives to natural enzymes owning to their exceptional attributes such as regulation of oxidative stress, convenient storage, adjustable catalytic activities, remarkable stability, and effortless scalability for large-scale production. Given the potent regulatory function of nanozymes on oxidative stress and coupled with the fact that reactive oxygen species (ROS) play a vital role in the occurrence and exacerbation of metabolic diseases, nanozyme offer a unique perspective for therapy through multifunctional activities, achieving essential results in the treatment of metabolic diseases by directly scavenging excess ROS or regulating pathologically related molecules. The rational design strategies, nanozyme-enabled therapeutic mechanisms at the cellular level, and the therapies of nanozyme for several typical metabolic diseases and underlying mechanisms are discussed, mainly including obesity, diabetes, cardiovascular disease, diabetic wound healing, and others. Finally, the pharmacokinetics, safety analysis, challenges, and outlooks for the application of nanozyme are also presented. This review will provide some instructive perspectives on nanozyme and promote the development of enzyme-mimicking strategies in metabolic disease therapy.
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Affiliation(s)
- Yanan Wang
- Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, No. 17 Qinghua East Road, Haidian District, Beijing, 100083, People's Republic of China
- Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety), The Ministry of Agriculture and Rural Affairs of the PR China, Beijing, China
| | - Xiaoyun He
- Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, No. 17 Qinghua East Road, Haidian District, Beijing, 100083, People's Republic of China
- Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety), The Ministry of Agriculture and Rural Affairs of the PR China, Beijing, China
| | - Kunlun Huang
- Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, No. 17 Qinghua East Road, Haidian District, Beijing, 100083, People's Republic of China.
- Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety), The Ministry of Agriculture and Rural Affairs of the PR China, Beijing, China.
| | - Nan Cheng
- Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, No. 17 Qinghua East Road, Haidian District, Beijing, 100083, People's Republic of China.
- Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety), The Ministry of Agriculture and Rural Affairs of the PR China, Beijing, China.
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Li Y, Xia X, Niu Z, Wang K, Liu J, Li X. hCeO 2@ Cu 5.4O nanoparticle alleviates inflammatory responses by regulating the CTSB-NLRP3 signaling pathway. Front Immunol 2024; 15:1344098. [PMID: 38711511 PMCID: PMC11070469 DOI: 10.3389/fimmu.2024.1344098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Accepted: 03/25/2024] [Indexed: 05/08/2024] Open
Abstract
Inflammatory responses, especially chronic inflammation, are closely associated with many systemic diseases. There are many ways to treat and alleviate inflammation, but how to solve this problem at the molecular level has always been a hot topic in research. The use of nanoparticles (NPs) as anti-inflammatory agents is a potential treatment method. We synthesized new hollow cerium oxide nanomaterials (hCeO2 NPs) doped with different concentrations of Cu5.4O NPs [the molar ratio of Cu/(Ce + Cu) was 50%, 67%, and 83%, respectively], characterized their surface morphology and physicochemical properties, and screened the safe concentration of hCeO2@Cu5.4O using the CCK8 method. Macrophages were cultured, and P.g-lipopolysaccharide-stimulated was used as a model of inflammation and co-cultured with hCeO2@Cu5.4O NPs. We then observe the effect of the transcription levels of CTSB, NLRP3, caspase-1, ASC, IL-18, and IL-1β by PCR and detect its effect on the expression level of CTSB protein by Western blot. The levels of IL-18 and IL-1β in the cell supernatant were measured by enzyme-linked immunosorbent assay. Our results indicated that hCeO2@Cu5.4O NPs could reduce the production of reactive oxygen species and inhibit CTSB and NLRP3 to alleviate the damage caused by the inflammatory response to cells. More importantly, hCeO2@Cu5.4O NPs showed stronger anti-inflammatory effects as Cu5.4O NP doping increased. Therefore, the development of the novel nanomaterial hCeO2@Cu5.4O NPs provides a possible new approach for the treatment of inflammatory diseases.
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Affiliation(s)
- Ying Li
- Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
- School of Stomatology, Qingdao University, Qingdao, China
| | - Xiaomin Xia
- Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
- School of Stomatology, Qingdao University, Qingdao, China
| | - Zhaojun Niu
- Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
- School of Stomatology, Qingdao University, Qingdao, China
| | - Ke Wang
- Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
- School of Stomatology, Qingdao University, Qingdao, China
| | - Jie Liu
- Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
- School of Stomatology, Qingdao University, Qingdao, China
| | - Xue Li
- Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
- School of Stomatology, Qingdao University, Qingdao, China
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20
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Singh S. Antioxidant nanozymes as next-generation therapeutics to free radical-mediated inflammatory diseases: A comprehensive review. Int J Biol Macromol 2024; 260:129374. [PMID: 38242389 DOI: 10.1016/j.ijbiomac.2024.129374] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 12/30/2023] [Accepted: 01/08/2024] [Indexed: 01/21/2024]
Abstract
Recent developments in exploring the biological enzyme mimicking properties in nanozymes have opened a separate avenue, which provides a suitable alternative to the natural antioxidants and enzymes. Due to high and tunable catalytic activity, low cost of synthesis, easy surface modification, and good biocompatibility, nanozymes have garnered significant research interest globally. Several inorganic nanomaterials have been investigated to exhibit catalytic activities of some of the key natural enzymes, including superoxide dismutase (SOD), catalase, glutathione peroxidase, peroxidase, and oxidase, etc. These nanozymes are used for diverse biomedical applications including therapeutics, imaging, and biosensing in various cells/tissues and animal models. In particular, inflammation-related diseases are closely associated with reactive oxygen and reactive nitrogen species, and therefore effective antioxidants could be excellent therapeutics due to their free radical scavenging ability. Although biological enzymes and other artificial antioxidants could perform well in scavenging the reactive oxygen and nitrogen species, however, suffer from several drawbacks such as the requirement of strict physiological conditions for enzymatic activity, limited stability in the environment beyond their optimum pH and temperature, and high cost of synthesis, purification, and storage make then unattractive for broad-spectrum applications. Therefore, this review systematically and comprehensively presents the free radical-mediated evolution of various inflammatory diseases (inflammatory bowel disease, mammary gland fibrosis, and inflammation, acute injury of the liver and kidney, mammary fibrosis, and cerebral ischemic stroke reperfusion) and their mitigation by various antioxidant nanozymes in the biological system. The mechanism of free radical scavenging by antioxidant nanozymes under in vitro and in vivo experimental models and catalytic efficiency comparison with corresponding natural enzymes has also been presented.
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Affiliation(s)
- Sanjay Singh
- National Institute of Animal Biotechnology (NIAB), Opposite Journalist Colony, Near Gowlidoddy, Extended Q-City Road, Gachibowli, Hyderabad 500032, Telangana, India.
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21
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Kim YG, Lee Y, Lee N, Soh M, Kim D, Hyeon T. Ceria-Based Therapeutic Antioxidants for Biomedical Applications. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2210819. [PMID: 36793245 DOI: 10.1002/adma.202210819] [Citation(s) in RCA: 56] [Impact Index Per Article: 56.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 01/20/2023] [Indexed: 06/18/2023]
Abstract
The growing interest in nanomedicine over the last 20 years has carved out a research field called "nanocatalytic therapy," where catalytic reactions mediated by nanomaterials are employed to intervene in disease-critical biomolecular processes. Among many kinds of catalytic/enzyme-mimetic nanomaterials investigated thus far, ceria nanoparticles stand out from others owing to their unique scavenging properties against biologically noxious free radicals, including reactive oxygen species (ROS) and reactive nitrogen species (RNS), by exerting enzyme mimicry and nonenzymatic activities. Much effort has been made to utilize ceria nanoparticles as self-regenerating antioxidative and anti-inflammatory agents for various kinds of diseases, given the detrimental effects of ROS and RNS therein that need alleviation. In this context, this review is intended to provide an overview as to what makes ceria nanoparticles merit attention in disease therapy. The introductory part describes the characteristics of ceria nanoparticles as an oxygen-deficient metal oxide. The pathophysiological roles of ROS and RNS are then presented, as well as their scavenging mechanisms by ceria nanoparticles. Representative examples of recent ceria-nanoparticle-based therapeutics are summarized by categorization into organ and disease types, followed by the discussion on the remaining challenges and future research directions.
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Affiliation(s)
- Young Geon Kim
- Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul, 08826, Republic of Korea
- School of Chemical and Biological Engineering, and Institute of Chemical Processes, Seoul National University, Seoul, 08826, Republic of Korea
| | - Yunjung Lee
- Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul, 08826, Republic of Korea
- School of Chemical and Biological Engineering, and Institute of Chemical Processes, Seoul National University, Seoul, 08826, Republic of Korea
| | - Nohyun Lee
- School of Advanced Materials Engineering, Kookmin University, Seoul, 02707, Republic of Korea
| | - Min Soh
- Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul, 08826, Republic of Korea
- Center for Advanced Pharmaceutical Technology, HyeonTechNBio, Inc., Seoul, 08826, Republic of Korea
| | - Dokyoon Kim
- Department of Bionano Engineering and Bionanotechnology, Hanyang University, Ansan, 15588, Republic of Korea
| | - Taeghwan Hyeon
- Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul, 08826, Republic of Korea
- School of Chemical and Biological Engineering, and Institute of Chemical Processes, Seoul National University, Seoul, 08826, Republic of Korea
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22
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Wang Y, Jia X, An S, Yin W, Huang J, Jiang X. Nanozyme-Based Regulation of Cellular Metabolism and Their Applications. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2301810. [PMID: 37017586 DOI: 10.1002/adma.202301810] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 03/29/2023] [Indexed: 06/19/2023]
Abstract
Metabolism is the sum of the enzyme-dependent chemical reactions, which produces energy in catabolic process and synthesizes biomass in anabolic process, exhibiting high similarity in mammalian cell, microbial cell, and plant cell. Consequently, the loss or gain of metabolic enzyme activity greatly affects cellular metabolism. Nanozymes, as emerging enzyme mimics with diverse functions and adjustable catalytic activities, have shown attractive potential for metabolic regulation. Although the basic metabolic tasks are highly similar for the cells from different species, the concrete metabolic pathway varies with the intracellular structure of different species. Here, the basic metabolism in living organisms is described and the similarities and differences in the metabolic pathways among mammalian, microbial, and plant cells and the regulation mechanism are discussed. The recent progress on regulation of cellular metabolism mainly including nutrient uptake and utilization, energy production, and the accompanied redox reactions by different kinds of oxidoreductases and their applications in the field of disease therapy, antimicrobial therapy, and sustainable agriculture is systematically reviewed. Furthermore, the prospects and challenges of nanozymes in regulating cell metabolism are also discussed, which broaden their application scenarios.
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Affiliation(s)
- Yue Wang
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China
- Research Center for Analytical Sciences, College of Chemistry, Nankai University, Tianjin, 300071, China
| | - Xiaodan Jia
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China
- Research Center for Analytical Sciences, College of Chemistry, Nankai University, Tianjin, 300071, China
| | - Shangjie An
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China (USTC), Hefei, Anhui, 230026, China
| | - Wenbo Yin
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China (USTC), Hefei, Anhui, 230026, China
| | - Jiahao Huang
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China (USTC), Hefei, Anhui, 230026, China
| | - Xiue Jiang
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China (USTC), Hefei, Anhui, 230026, China
- Research Center for Analytical Sciences, College of Chemistry, Nankai University, Tianjin, 300071, China
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Liu Y, Huang J, Li S, Li Z, Chen C, Qu G, Chen K, Teng Y, Ma R, Wu X, Ren J. Advancements in hydrogel-based drug delivery systems for the treatment of inflammatory bowel disease: a review. Biomater Sci 2024; 12:837-862. [PMID: 38196386 DOI: 10.1039/d3bm01645e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2024]
Abstract
Inflammatory bowel disease (IBD) is a chronic disorder that affects millions of individuals worldwide. However, current drug therapies for IBD are plagued by significant side effects, low efficacy, and poor patient compliance. Consequently, there is an urgent need for novel therapeutic approaches to alleviate IBD. Hydrogels, three-dimensional networks of hydrophilic polymers with the ability to swell and retain water, have emerged as promising materials for drug delivery in the treatment of IBD due to their biocompatibility, tunability, and responsiveness to various stimuli. In this review, we summarize recent advancements in hydrogel-based drug delivery systems for the treatment of IBD. We first identify three pathophysiological alterations that need to be addressed in the current treatment of IBD: damage to the intestinal mucosal barrier, dysbiosis of intestinal flora, and activation of inflammatory signaling pathways leading to disequilibrium within the intestines. Subsequently, we discuss in depth the processes required to prepare hydrogel drug delivery systems, from the selection of hydrogel materials, types of drugs to be loaded, methods of drug loading and drug release mechanisms to key points in the preparation of hydrogel drug delivery systems. Additionally, we highlight the progress and impact of the hydrogel-based drug delivery system in IBD treatment through regulation of physical barrier immune responses, promotion of mucosal repair, and improvement of gut microbiota. In conclusion, we analyze the challenges of hydrogel-based drug delivery systems in clinical applications for IBD treatment, and propose potential solutions from our perspective.
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Affiliation(s)
- Ye Liu
- School of Medicine, Southeast University, Nanjing, 210009, China
- Research Institute of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China.
| | - Jinjian Huang
- Research Institute of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China.
| | - Sicheng Li
- Research Institute of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China.
| | - Ze Li
- Research Institute of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China.
| | - Canwen Chen
- Research Institute of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China.
| | - Guiwen Qu
- School of Medicine, Southeast University, Nanjing, 210009, China
- Research Institute of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China.
| | - Kang Chen
- Research Institute of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China.
| | - Yitian Teng
- Research Institute of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China.
| | - Rui Ma
- School of Medicine, Southeast University, Nanjing, 210009, China
- Research Institute of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China.
| | - Xiuwen Wu
- School of Medicine, Southeast University, Nanjing, 210009, China
- Research Institute of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China.
| | - Jianan Ren
- School of Medicine, Southeast University, Nanjing, 210009, China
- Research Institute of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China.
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Li Q, Lin L, Zhang C, Zhang H, Ma Y, Qian H, Chen XL, Wang X. The progression of inorganic nanoparticles and natural products for inflammatory bowel disease. J Nanobiotechnology 2024; 22:17. [PMID: 38172992 PMCID: PMC10763270 DOI: 10.1186/s12951-023-02246-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 12/03/2023] [Indexed: 01/05/2024] Open
Abstract
There is a growing body of evidence indicating a close association between inflammatory bowel disease (IBD) and disrupted intestinal homeostasis. Excessive production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with an increase in M1 proinflammatory macrophage infiltration during the activation of intestinal inflammation, plays a pivotal role in disrupting intestinal homeostasis in IBD. The overabundance of ROS/RNS can cause intestinal tissue damage and the disruption of crucial gut proteins, which ultimately compromises the integrity of the intestinal barrier. The proliferation of M1 macrophages contributes to an exaggerated immune response, further compromising the intestinal immune barrier. Currently, intestinal nanomaterials have gained widespread attention in the context of IBD due to their notable characteristics, including the ability to specifically target regions of interest, clear excess ROS/RNS, and mimic biological enzymes. In this review, we initially elucidated the gut microenvironment in IBD. Subsequently, we delineate therapeutic strategies involving two distinct types of nanomedicine, namely inorganic nanoparticles and natural product nanomaterials. Finally, we present a comprehensive overview of the promising prospects associated with the application of nanomedicine in future clinical settings for the treatment of IBD (graphic abstract). Different classes of nanomedicine are used to treat IBD. This review primarily elucidates the current etiology of inflammatory bowel disease and explores two prominent nanomaterial-based therapeutic approaches. First, it aims to eliminate excessive reactive oxygen species and reactive nitrogen species. Second, they focus on modulating the polarization of inflammatory macrophages and reducing the proportion of pro-inflammatory macrophages. Additionally, this article delves into the treatment of inflammatory bowel disease using inorganic metal nanomaterials and natural product nanomaterials.
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Affiliation(s)
- Qingrong Li
- Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, People's Republic of China
| | - Liting Lin
- School of Biomedical Engineering, Research and Engineering Center of Biomedical Materials, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei, 230032, People's Republic of China
| | - Cong Zhang
- Division of Gastroenterology, Division of Life Science and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, 230026, People's Republic of China
| | - Hengguo Zhang
- Key Laboratory of Oral Diseases Research of Anhui Province, College and Hospital of Stomatology, Anhui Medical University, Hefei, 230032, People's Republic of China
| | - Yan Ma
- Division of Gastroenterology, Division of Life Science and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, 230026, People's Republic of China
| | - Haisheng Qian
- Division of Gastroenterology, Division of Life Science and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, 230026, People's Republic of China.
| | - Xu-Lin Chen
- Department of Burns, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People's Republic of China.
| | - Xianwen Wang
- Division of Gastroenterology, Division of Life Science and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, 230026, People's Republic of China.
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25
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Min DK, Kim YE, Kim MK, Choi SW, Park N, Kim J. Orally Administrated Inflamed Colon-Targeted Nanotherapeutics for Inflammatory Bowel Disease Treatment by Oxidative Stress Level Modulation in Colitis. ACS NANO 2023; 17:24404-24416. [PMID: 38039189 DOI: 10.1021/acsnano.3c11089] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/03/2023]
Abstract
Inflammatory bowel disease (IBD) is characterized by an inappropriate and persistent inflammatory immune response and is often accompanied by excessive reactive oxygen species (ROS) production. For effective IBD treatment, there is a high demand for safe and targeted therapy that can be orally administered. In this study, we aimed to propose the use of inflamed colon-targeted antioxidant nanotherapeutics (ICANs) for in situ oxidative stress level modulation in colitis. ICANs consist of mesoporous silica nanoparticles (MSNs) with surface-attached ROS-scavenging ceria nanoparticles (CeNPs), which are further coated with poly(acrylic acid) (PAA) to facilitate preferential adherence to inflamed colon tissues through electrostatic interaction. We achieved a high ROS-scavenging property that remained effective even after artificial gastrointestinal fluid incubation by optimization of the molecular weight and PAA-coating pH. The orally administered ICANs demonstrated enhanced adherence to inflamed colon tissues in an acute inflammation mouse model of IBD induced by dextran sulfate sodium. This targeted delivery resulted in gut microenvironment modulation by regulating redox balance and reducing inflammatory cell infiltration, thereby suppressing the colitis-associated immune response. These findings highlight the potential of noninvasive ICANs as a promising candidate for treating inflammatory intestinal diseases by oxidative stress level modulation in colitis.
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Affiliation(s)
- Dong Kwang Min
- School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
| | - Ye Eun Kim
- School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
| | - Min Kyung Kim
- Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
| | - Seung Woo Choi
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea
| | - Nuri Park
- School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
| | - Jaeyun Kim
- School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
- Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
- Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
- Institute of Quantum Biophysics (IQB), Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
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Wang H, Wang L, Chen Y, Huang J, Xing Y, Wang L, Zhang J, Yang H. Catalytically proficient ceria nanodots supported on redox-active mesoporous hosts for treatment of inflammatory bowel disease via efficient ROS scavenging. J Mater Chem B 2023; 11:10369-10382. [PMID: 37873599 DOI: 10.1039/d3tb01602a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2023]
Abstract
Ceria nanozyme-based ROS scavengers have shown great potential in the treatment of inflammatory bowel disease (IBD) through microenvironment regulation. However, the currently developed nanotherapeutics suffer from difficulties in concomitantly achieving small sizes and stable interparticle dispersion which is pivotal to sufficient oxygen vacancies facilitating electron transfer and oxygen storage in the dynamic cycling of Ce3+/Ce4+ redox pairs. Herein, a hybrid nanosystem consisting of ceria nanodots supported on redox-active mesoporous hosts was developed to address the challenge of ROS scavenging, in particular the efficient downregulation of the readily renewable, highly concentrated H2O2 species. Specifically, Ce4+ ions oxidized from Ce3+ in weakly basic solution were captured and reduced in time by the abundant catechols on the mesoporous polydopamine nanoparticles. This led to strong restriction of ceria growth (∼2.8 nm) in the ion precipitation process and efficient maintenance of the Ce3+/Ce4+ ratio at a high value of 1.59 which is 4.8 fold higher than that of homogeneously nucleated ceria nanoparticles. Through this design, the nanohybrid showed an attractive catalytic performance in scavenging multiple ROS species, particularly the fast and recyclable conversion of H2O2. Thereby, significant suppression of the inflammatory cytokine/chemokine secretion was achieved by inhibiting the activation of NF-κB signaling pathways (5.1 fold higher as compared to those of pristine ceria nanoparticles), upregulating the Nrf2 signaling pathway, and reducing the proportion of M1 macrophages at IBD sites. Therapeutic efficiency was also demonstrated by the effective repair of the intestinal mucosal barrier by recovering the tight junction integrity in vivo. This study sheds light on the employment of redox-active hosts to support ceria catalysts for advancing anti-inflammation applications by boosting ROS scavenging performance.
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Affiliation(s)
- Hailing Wang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing 400044, China.
| | - Liucan Wang
- Department of General Surgery, Chongqing People's Hospital, No. 118, Xingguang Avenue, Liangjiang New Area, Chongqing 401121, China.
| | - Yuhua Chen
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing 400044, China.
| | - Jixi Huang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing 400044, China.
| | - Yuxin Xing
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing 400044, China.
| | - Lu Wang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing 400044, China.
| | - Jixi Zhang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing 400044, China.
| | - Hua Yang
- Department of General Surgery, Chongqing People's Hospital, No. 118, Xingguang Avenue, Liangjiang New Area, Chongqing 401121, China.
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Yan S, Gao Z, Ding J, Chen S, Wang Z, Jin W, Qu B, Zhang Y, Yang L, Guo D, Yin T, Yang Y, Zhang Y, Yang J. Nanocomposites based on nanoceria regulate the immune microenvironment for the treatment of polycystic ovary syndrome. J Nanobiotechnology 2023; 21:412. [PMID: 37936120 PMCID: PMC10631133 DOI: 10.1186/s12951-023-02182-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 10/26/2023] [Indexed: 11/09/2023] Open
Abstract
The immune system is closely associated with the pathogenesis of polycystic ovary syndrome (PCOS). Macrophages are one of the important immune cell types in the ovarian proinflammatory microenvironment, and ameliorate the inflammatory status mainly through M2 phenotype polarization during PCOS. Current therapeutic approaches lack efficacy and immunomodulatory capacity, and a new therapeutic method is needed to prevent inflammation and alleviate PCOS. Here, octahedral nanoceria nanoparticles with powerful antioxidative ability were bonded to the anti-inflammatory drug resveratrol (CeO2@RSV), which demonstrates a crucial strategy that involves anti-inflammatory and antioxidative efficacy, thereby facilitating the proliferation of granulosa cells during PCOS. Notably, our nanoparticles were demonstrated to possess potent therapeutic efficacy via anti-inflammatory activities and effectively alleviated endocrine dysfunction, inflammation and ovarian injury in a dehydroepiandrosterone (DHEA)-induced PCOS mouse model. Collectively, this study revealed the tremendous potential of the newly developed nanoparticles in ameliorating the proinflammatory microenvironment and promoting the function of granulosa cells, representing the first attempt to treat PCOS by using CeO2@RSV nanoparticles and providing new insights in combating clinical PCOS.
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Affiliation(s)
- Sisi Yan
- Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, 430060, China
| | - Zhipeng Gao
- Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, People's Republic of China
| | - Jinli Ding
- Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, 430060, China
| | - Suming Chen
- The Institute for Advanced Studies, Wuhan University, Wuhan, China
| | - Zehao Wang
- Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, 430060, China
| | - Wenyi Jin
- Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, 430060, China
| | - Bing Qu
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yi Zhang
- Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, 430060, China
| | - Lian Yang
- Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, 430060, China
| | - Duanying Guo
- Longgang District People's Hospital of Shenzhen, Shenzhen, China.
| | - Tailang Yin
- Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, 430060, China.
| | - Yanbing Yang
- Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, People's Republic of China.
| | - Yan Zhang
- Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
| | - Jing Yang
- Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, 430060, China.
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Fu W, Xu L, Chen Z, Kan L, Ma Y, Qian H, Wang W. Recent advances on emerging nanomaterials for diagnosis and treatment of inflammatory bowel disease. J Control Release 2023; 363:149-179. [PMID: 37741461 DOI: 10.1016/j.jconrel.2023.09.033] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Revised: 09/16/2023] [Accepted: 09/18/2023] [Indexed: 09/25/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disorder that affects the entire gastrointestinal tract and is associated with an increased risk of colorectal cancer. Mainstream clinical testing methods are time-consuming, painful for patients, and insufficiently sensitive to detect early symptoms. Currently, there is no definitive cure for IBD, and frequent doses of medications with potentially severe side effects may affect patient response. In recent years, nanomaterials have demonstrated considerable potential for IBD management due to their diverse structures, composition, and physical and chemical properties. In this review, we provide an overview of the advances in nanomaterial-based diagnosis and treatment of IBD in recent five years. Multi-functional bio-nano platforms, including contrast agents, near-infrared (NIR) fluorescent probes, and bioactive substance detection agents have been developed for IBD diagnosis. Based on a series of pathogenic characteristics of IBD, the therapeutic strategies of antioxidant, anti-inflammatory, and intestinal microbiome regulation of IBD based on nanomaterials are systematically introduced. Finally, the future challenges and prospects in this field are presented to facilitate the development of diagnosis and treatment of IBD.
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Affiliation(s)
- Wanyue Fu
- School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei 230032, PR China; Anhui Engineering Research Center for Medical Micro-Nano Devices, Hefei, Anhui 230012, China
| | - Lingling Xu
- School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei 230032, PR China; Anhui Engineering Research Center for Medical Micro-Nano Devices, Hefei, Anhui 230012, China
| | - Zetong Chen
- School of Stomatology, Anhui Medical University, Hefei, Anhui 230032, PR China
| | - Lingling Kan
- School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei 230032, PR China; Anhui Engineering Research Center for Medical Micro-Nano Devices, Hefei, Anhui 230012, China
| | - Yan Ma
- School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei 230032, PR China; Anhui Engineering Research Center for Medical Micro-Nano Devices, Hefei, Anhui 230012, China.
| | - Haisheng Qian
- School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei 230032, PR China; Anhui Engineering Research Center for Medical Micro-Nano Devices, Hefei, Anhui 230012, China.
| | - Wanni Wang
- School of Biomedical Engineering, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei 230032, PR China; Anhui Engineering Research Center for Medical Micro-Nano Devices, Hefei, Anhui 230012, China.
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Wang X, Jiao M, Tian F, Lu X, Xiong H, Liu F, Wan Y, Zhang X, Wan H. A Biomimetic Nanoplatform with Improved Inflammatory Targeting Behavior for ROS Scavenging-Based Treatment of Ulcerative Colitis. Adv Healthc Mater 2023; 12:e2301450. [PMID: 37537878 DOI: 10.1002/adhm.202301450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 07/23/2023] [Indexed: 08/05/2023]
Abstract
Ulcerative colitis (UC), a refractory disease, has become a global problem. Herein, a biomimetic nanoplatform (AU-LIP-CM) comprising Au cluster enzymes (AU)-loaded liposomes (AU-LIP) camouflaged with the fusion membrane (CM) consisting of neutrophil (NC) and red blood cell (RBC) membrane is designed for the treatment of UC. Briefly, revealed by second near-infrared (NIR-II) imaging through collection of fluorescence emitting >1200 nm from AU, the improved inflammatory targeting behavior contributed by CM cloaking, which inherits abilities of inflammatory targeting and immune escape from NC and RBC, respectively, promotes specific accumulation of AU within inflammatory intestines with up to ≈11.5 times higher than that of bare AU. Afterward, AU possessing superoxide dismutase- and catalase-like activities realizes high-efficiency scavenging of reactive oxygen species (ROS), leading to repair of intestinal barriers, regulation of the immune system, and modulation of gut microbiota, which surpass first-line UC drug. In addition, study of underlying therapeutic mechanism demonstrated that the treatment with AU-LIP-CM can alter the gene signature associated with response to ROS for UC mice to a profile similar to that of healthy mice, deciphering related signal pathways. The strategy developed here provides insights of learning from properties of natural bio-substances to empower biomimetic nanoplatform to confront diseases.
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Affiliation(s)
- Xiaofen Wang
- School of Chemistry and Chemical Engineering, Nanchang University, Nanchang, 330031, China
| | - Menglu Jiao
- Department of Physics and Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, School of Sciences, Tianjin University, Tianjin, 300350, China
| | - Fangzhen Tian
- Tianjin Key Laboratory of Brain Science and Neural Engineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China
| | - Xuan Lu
- College of Food Science and Technology, Nanchang University, Nanchang, 330031, China
| | - Huihuang Xiong
- School of Chemistry and Chemical Engineering, Nanchang University, Nanchang, 330031, China
| | - Fan Liu
- Center of Analysis and Testing, Nanchang University, Nanchang, 330047, China
| | - Yiqun Wan
- School of Chemistry and Chemical Engineering, Nanchang University, Nanchang, 330031, China
| | - Xiaodong Zhang
- Department of Physics and Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, School of Sciences, Tianjin University, Tianjin, 300350, China
- Tianjin Key Laboratory of Brain Science and Neural Engineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China
| | - Hao Wan
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, 330047, China
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Liu C, Wang Q, Wu YL. Recent Advances in Nanozyme-Based Materials for Inflammatory Bowel Disease. Macromol Biosci 2023; 23:e2300157. [PMID: 37262405 DOI: 10.1002/mabi.202300157] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 05/07/2023] [Indexed: 06/03/2023]
Abstract
Inflammatory bowel disease (IBD) is a type of chronic inflammatory disorder that interferes with the patient's lifestyle and, in extreme situations, can be deadly. Fortunately, with the ever-deepening understanding of the pathological cause of IBD, recent studies using nanozyme-based materials have indicated the potential toward effective IBD treatment. In this review, the recent advancement of nanozymes for the treatment of enteritis is summarized from the perspectives of the structural design of nanozyme-based materials and therapeutic strategies, intending to serve as a reference to produce effective nanozymes for moderating inflammation in the future. Last but not least, the potential and current restrictions for using nanozymes in IBD will also be discussed. In short, this review may provide a guidance for the development of innovative enzyme-mimetic nanomaterials that offer a novel and efficient approach toward the effective treatment of IBD.
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Affiliation(s)
- Chuyi Liu
- Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361102, China
| | - Qi Wang
- Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361102, China
| | - Yun-Long Wu
- Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361102, China
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31
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Zhang Y, Lei H, Wang P, Zhou Q, Yu J, Leng X, Ma R, Wang D, Dong K, Xing J, Dong Y. Restoration of dysregulated intestinal barrier and inflammatory regulation through synergistically ameliorating hypoxia and scavenging reactive oxygen species using ceria nanozymes in ulcerative colitis. Biomater Res 2023; 27:75. [PMID: 37507801 PMCID: PMC10375752 DOI: 10.1186/s40824-023-00412-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 07/09/2023] [Indexed: 07/30/2023] Open
Abstract
BACKGROUND Reactive oxygen species (ROS) overproduction and excessive hypoxia play pivotal roles in the initiation and progression of ulcerative colitis (UC). Synergistic ROS scavenging and generating O2 could be a promising strategy for UC treatment. METHODS Ceria nanozymes (PEG-CNPs) are fabricated using a modified reverse micelle method. We investigate hypoxia attenuating and ROS scavenging of PEG-CNPs in intestinal epithelial cells and RAW 264.7 macrophages and their effects on pro-inflammatory macrophages activation. Subsequently, we investigate the biodistribution, pharmacokinetic properties and long-term toxicity of PEG-CNPs in mice. PEG-CNPs are administered intravenously to mice with 2,4,6-trinitrobenzenesulfonic acid-induced colitis to test their colonic tissue targeting and assess their anti-inflammatory activity and mucosal healing properties in UC. RESULTS PEG-CNPs exhibit multi-enzymatic activity that can scavenge ROS and generate O2, promote intestinal epithelial cell healing and inhibit pro-inflammatory macrophage activation, and have good biocompatibility. After intravenous administration of PEG-CNPs to colitis mice, they can enrich at the site of colonic inflammation, and reduce hypoxia-induced factor-1α expression in intestinal epithelial cells by scavenging ROS to generate O2, thus further promoting disrupted intestinal mucosal barrier restoration. Meanwhile, PEG-CNPs can effectively scavenge ROS in impaired colon tissues and relieve colonic macrophage hypoxia to suppress the pro-inflammatory macrophages activation, thereby preventing UC occurrence and development. CONCLUSION This study has provided a paradigm to utilize metallic nanozymes, and suggests that further materials engineering investigations could yield a facile method based on the pathological characteristics of UC for clinically managing UC.
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Affiliation(s)
- Ying Zhang
- Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
- Department of Pharmaceutics, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
| | - Hengyu Lei
- Department of Pharmaceutics, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
| | - Pengchong Wang
- Department of Pharmacy, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China
| | - Qinyuan Zhou
- Department of Pharmaceutics, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
| | - Jie Yu
- Department of Pharmaceutics, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
| | - Xue Leng
- Department of Pharmaceutics, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
| | - Ruirui Ma
- Department of Pharmaceutics, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
| | - Danyang Wang
- Department of Pharmaceutics, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
| | - Kai Dong
- Department of Pharmaceutics, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
| | - Jianfeng Xing
- Department of Pharmaceutics, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
| | - Yalin Dong
- Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
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32
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Bi J, Mo C, Li S, Huang M, Lin Y, Yuan P, Liu Z, Jia B, Xu S. Immunotoxicity of metal and metal oxide nanoparticles: from toxic mechanisms to metabolism and outcomes. Biomater Sci 2023. [PMID: 37161951 DOI: 10.1039/d3bm00271c] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/11/2023]
Abstract
The influence of metal and metal oxide nanomaterials on various fields since their discovery has been remarkable. They have unique properties, and therefore, have been employed in specific applications, including biomedicine. However, their potential health risks cannot be ignored. Several studies have shown that exposure to metal and metal oxide nanoparticles can lead to immunotoxicity. Different types of metals and metal oxide nanoparticles may have a negative impact on the immune system through various mechanisms, such as inflammation, oxidative stress, autophagy, and apoptosis. As an essential factor in determining the function and fate of immune cells, immunometabolism may also be an essential target for these nanoparticles to exert immunotoxic effects in vivo. In addition, the biodegradation and metabolic outcomes of metal and metal oxide nanoparticles are also important considerations in assessing their immunotoxic effects. Herein, we focus on the cellular mechanism of the immunotoxic effects and toxic effects of different types of metal and metal oxide nanoparticles, as well as the metabolism and outcomes of these nanoparticles in vivo. Also, we discuss the relationship between the possible regulatory effect of nanoparticles on immunometabolism and their immunotoxic effects. Finally, we present perspectives on the future research and development direction of metal and metal oxide nanomaterials to promote scientific research on the health risks of nanomaterials and reduce their adverse effects on human health.
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Affiliation(s)
- Jiaming Bi
- Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, China.
| | - Chuzi Mo
- Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, China.
| | - Siwei Li
- Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, China.
| | - Mingshu Huang
- Department of Oral and Maxillofacial Surgery, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, China.
| | - Yunhe Lin
- Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, China.
| | - Peiyan Yuan
- Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, China.
| | - Zhongjun Liu
- Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, China.
| | - Bo Jia
- Department of Oral and Maxillofacial Surgery, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, China.
| | - Shuaimei Xu
- Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, China.
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33
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Pu Y, Fan X, Zhang Z, Guo Z, Pan Q, Gao W, Luo K, He B. Harnessing polymer-derived drug delivery systems for combating inflammatory bowel disease. J Control Release 2023; 354:1-18. [PMID: 36566845 DOI: 10.1016/j.jconrel.2022.12.044] [Citation(s) in RCA: 53] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 12/18/2022] [Accepted: 12/20/2022] [Indexed: 12/27/2022]
Abstract
The inflammatory bowel disease (IBD) is incurable, chronic, recrudescent disorders in the inflamed intestines. Current clinic treatments are challenged by systemic exposure-induced severe side effects, inefficiency after long-term treatment, and increased risks of infection and malignancy due to immunosuppression. Fortunately, naturally bioactive small molecules, reactive oxygen species scavengers (or antioxidants), and gut microbiota modulators have emerged as promising candidates for the IBD treatment. Polymeric systems have been engineered as a delivery vehicle to improve the bioavailability and efficacy of these therapeutic agents through targeting the mucosa and enhancing intestinal adhesion and retention, and reduce their systemic toxicity. Herein we survey polymer-derived drug delivery systems for combating the IBD. Advanced delivery technologies, therapeutic intervention strategies, and the principles for the construction of hierarchical, mucosa-targeting, and bioresponsive systems are elaborated, providing insights into design and development of from-bench-to-bedside drug delivery polymeric systems for the IBD treatment.
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Affiliation(s)
- Yuji Pu
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
| | - Xi Fan
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
| | - Zhuangzhuang Zhang
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
| | - Zhaoyuan Guo
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
| | - Qingqing Pan
- School of Preclinical Medicine, Chengdu University, Chengdu 610106, China
| | - Wenxia Gao
- College of Chemistry & Materials Engineering, Wenzhou University, Wenzhou 325027, China
| | - Kui Luo
- Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital, Functional and Molecular Imaging Key Laboratory of Sichuan Province, Sichuan University, Chengdu 610041, China
| | - Bin He
- National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, China.
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34
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Lu Y, Cao C, Pan X, Liu Y, Cui D. Structure design mechanisms and inflammatory disease applications of nanozymes. NANOSCALE 2022; 15:14-40. [PMID: 36472125 DOI: 10.1039/d2nr05276h] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Nanozymes are artificial enzymes with high catalytic activity, low cost, and good biocompatibility, and have received ever-increasing attention in recent years. Various inorganic and organic nanoparticles have been found to exhibit enzyme-like activities and are used as nanozymes for diverse biomedical applications ranging from tumor imaging and therapeutics to detection. However, their further clinical applications are hindered by the potential toxicity and long-term retention of nanomaterials in vivo. Clarifying the catalytic mechanism of nanozymes and identifying the key factors responsible for their behavior can guide the design of nanozyme structure, enlighten the ways to improve their enzyme-like activities, and minimize the dosage of nanozymes, leading to reduced toxicity to the human body for a real biomedical application prospect. In particular, inflammation occurring in numerous diseases is closely related to reactive oxygen species, and the active oxygen scavenging ability of nanozymes potentially exerts excellent therapeutic effects on inflammatory diseases. In this review, we systematically summarize the structure-activity relationship of nanozymes, including regulation strategies for size and morphology, surface structure, and composition. Based on the structure-activity mechanisms, a series of chemically designed nanozymes developed to target various inflammatory diseases are briefly summarized.
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Affiliation(s)
- Yi Lu
- Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, People's Republic of China.
| | - Cheng Cao
- Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, People's Republic of China.
| | - Xinni Pan
- Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yanlei Liu
- Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, People's Republic of China.
| | - Daxiang Cui
- Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, People's Republic of China.
- National Engineering Center for Nanotechnology, Shanghai 200240, People's Republic of China.
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35
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Ye H, Ma Z, Liu L, Zhang T, Han Q, Xiang Z, Xia Y, Ke Y, Guan X, Shi Q, Ataullakhanov FI, Panteleev M. Thrombus Inhibition and Neuroprotection for Ischemic Stroke Treatment through Platelet Regulation and ROS Scavenging. ChemMedChem 2022; 17:e202200317. [PMID: 36220787 DOI: 10.1002/cmdc.202200317] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 10/09/2022] [Indexed: 01/14/2023]
Abstract
Ischemic stroke is caused by cerebrovascular stenosis or occlusion. Excessive reactive oxygen species (ROS) are the focus-triggering factor of irreversible injury in ischemic regions, which result in harmful cascading effects to brain tissue, such as inflammation and microthrombus formation. In the present work, we designed nanodelivery systems (NDSs) based on MnO2 loaded with Ginkgolide B (GB) for restoring the intracerebral microenvironment in ischemic stroke, such as ROS scavenging, O2 elevation, thrombus inhibition and damage repair. GB can activate the endogenous antioxidant defense of cells by enhancing the nuclear factor-E2-related factor 2 (Nrf2) signalling pathway, thus protecting brain tissue from oxidative damage. However, the blood-brain barrier (BBB) is also a therapeutic obstacle for the delivery of these agents to ischemic regions. MnO2 nanoparticles have an inherent BBB penetration effect, which enhances the delivery of therapeutic agents within brain tissue. MnO2 , with mimicking enzymatic activity, can catalyze the decomposition of overproduced H2 O2 in the ischemic microenvironment to O2 , meanwhile releasing platelet-antagonizing GB molecules, thus alleviating cerebral hypoxia, oxidative stress damage, and microthrombus generation. This study may provide a promising therapeutic route for regulating the microenvironment of ischemic stroke through a combined function of ROS scavenging, microthrombus inhibition, and BBB penetration.
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Affiliation(s)
- Hongbo Ye
- Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, P. R. China
| | - Zhifang Ma
- Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, P. R. China
| | - Lei Liu
- Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, P. R. China.,University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China
| | - Tianci Zhang
- Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, P. R. China.,University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China
| | - Qiaoyi Han
- Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, P. R. China.,University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China
| | - Zehong Xiang
- Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, P. R. China.,University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China
| | - Yu Xia
- Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, P. R. China.,University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China
| | - Yue Ke
- Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, P. R. China.,University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China
| | - Xinghua Guan
- Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, P. R. China
| | - Qiang Shi
- Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, P. R. China.,University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China.,Key Laboratory of Polymeric Materials Design and Synthesis for Biomedical Function, Soochow University, Suzhou, Jiangsu, 215123, P. R. China
| | - Fazly I Ataullakhanov
- Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, 117198, Russia.,Faculty of Physics, Lomonosov Moscow State University, Moscow, 119991, Russia
| | - Mikhail Panteleev
- Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, 117198, Russia
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36
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37
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Huang L, Wang J, Kong L, Wang X, Li Q, Zhang L, Shi J, Duan J, Mu H. ROS-responsive hyaluronic acid hydrogel for targeted delivery of probiotics to relieve colitis. Int J Biol Macromol 2022; 222:1476-1486. [PMID: 36195227 DOI: 10.1016/j.ijbiomac.2022.09.247] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 09/23/2022] [Accepted: 09/27/2022] [Indexed: 11/05/2022]
Abstract
Probiotics are generally used as therapeutic intervention in inflammatory bowel disease. However, the low survival rate in harsh gastrointestinal environment and limited retention in intestine greatly restrict their health benefits. To address this problem, a ROS-responsive hydrogel based on hyaluronic acid (HA) was developed for encapsulation and targeted delivery of probiotics. The hydrogel was prepared facilely by physiological crosslink with methacrylated HA and thiolated thioketal. As a model probiotic, Lactobacillu reuteri showed a significantly increased survival rate in simulated digestive conditions after encapsulated in hydrogel. The negative properties conferred the hydrogel preferential adhesions to inflammation sites. Meanwhile, the excess reactive oxygen species (ROS) produced by inflamed colon tissues selectively cleaved thioketal linkages resulted in hydrogel degradation and local probiotics release. Furthermore, the hydrogel exerted an appropriate ROS-scavenge capacity and protected HT-29 cells from oxidative damage. Animal experiments indicated that hydrogel-encapsulated L. reuteri could remarkably alleviate the symptoms and improve the survival rate of mice with dextran sulfate sodium (DSS)-induced colitis. These results suggested that the biocompatible hydrogel may be a delivery platform to target inflamed intestines and expand the application of probiotics as pharmaceuticals.
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Affiliation(s)
- Lijie Huang
- College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, Shaanxi, China
| | - Junjie Wang
- College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, Shaanxi, China
| | - Lili Kong
- College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, Shaanxi, China
| | - Xing Wang
- College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, Shaanxi, China
| | - Qiulei Li
- College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, Shaanxi, China
| | - Lingjiao Zhang
- College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, Shaanxi, China
| | - Jingru Shi
- College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, Shaanxi, China
| | - Jinyou Duan
- College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, Shaanxi, China
| | - Haibo Mu
- College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, Shaanxi, China.
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