Reactive Oxygen Species-Responsive Polyether Micelle Nanomaterials for Targeted Treatment of Ulcerative Colitis

Zhao, Xinxin; Ma, Shanbo; Wen, Jinpeng; Hu, Datao; Gao, Jushan; Peng, Qiao; Zhang, Yuchen; Wang, Jinqing; Wang, Ke; Shi, Xiaopeng

doi:10.1166/jbn.2022.3233

Cited by 6 publications

(1 citation statement)

References 37 publications

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“…Among immunomodulatory factors, the inflammatory response is considered a central mechanism in the pathophysiology of UC, and pro-inflammatory cytokines play an active role in the inflammatory response by inducing macrophage migration and the release of inflammatory mediators, which further amplify the inflammatory response (Zhao et al, 2022 ). NF-κB plays a central role in regulating the inflammatory process (Lee et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Integrative analysis revealed the role of glucagon-like peptide-2 in improving experimental colitis in mice by inhibiting inflammatory pathways, regulating glucose metabolism, and modulating gut microbiota

Gao

Cui

et al. 2023

Front. Microbiol.

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IntroductionUlcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent and remitting inflammation of the mucosa of the colon and rectum, the incidence of which is on the rise. Glucagon-like peptide-2 (GLP-2) is a newly discovered neurotrophic factor, but its efficacy and mechanism of action in UC remain unclear. In this study, we investigated the protective effects and potential targets of GLP-2 on dextran sodium sulfate (DSS)-induced UC in mice through integrative analysis.MethodsThe effects of GLP-2 on UC were assessed by calculating the disease activity index, colonic mucosal damage index, and pathological histological scores. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to detect the expression of GLP-2, nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3). The 16SrRNA gene was used to detect changes in gut microbiota in mouse colonic tissues, and oral glucose tolerance test (OGTT) blood glucose levels were used to analyze the differences in flora.ResultsThe results showed that GLP-2 could reduce the inflammation of UC mice, which may be achieved by inhibiting the potential targets of NF-κB, and Janus kinase (JAK)/STAT3 inflammatory pathways, regulating sugar metabolism, increasing dominant species, and improving microbial diversity.DiscussionThis study provides new insight into the potential of GLP-2 for achieving more ideal UC treatment goals in future.

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Section: Discussionmentioning

confidence: 99%

Integrative analysis revealed the role of glucagon-like peptide-2 in improving experimental colitis in mice by inhibiting inflammatory pathways, regulating glucose metabolism, and modulating gut microbiota

Gao

Cui

et al. 2023

Front. Microbiol.

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Responsive nanosystems for targeted therapy of ulcerative colitis: Current practices and future perspectives

et al. 2023

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The pharmacological approach to treating gastrointestinal diseases is suffering from various challenges. Among such gastrointestinal diseases, ulcerative colitis manifests inflammation at the colon site specifically. Patients suffering from ulcerative colitis notably exhibit thin mucus layers that offer increased permeability for the attacking pathogens. In the majority of ulcerative colitis patients, the conventional treatment options fail in controlling the symptoms of the disease leading to distressing effects on the quality of life. Such a scenario is due to the failure of conventional therapies to target the loaded moiety into specific diseased sites in the colon. Targeted carriers are needed to address this issue and enhance the drug effects. Conventional nanocarriers are mostly readily cleared and have nonspecific targeting. To accumulate the desired concentration of the therapeutic candidates at the inflamed area of the colon, smart nanomaterials with responsive nature have been explored recently that include pH responsive, reactive oxygen species responsive (ROS), enzyme responsive and thermo – responsive smart nanocarrier systems. The formulation of such responsive smart nanocarriers from nanotechnology scaffolds has resulted in the selective release of therapeutic drugs, avoiding systemic absorption and limiting the undesired delivery of targeting drugs into healthy tissues. Recent advancements in the field of responsive nanocarrier systems have resulted in the fabrication of multi-responsive systems i.e. dual responsive nanocarriers and derivitization that has increased the biological tissues and smart nanocarrier’s interaction. In addition, it has also led to efficient targeting and significant cellular uptake of the therapeutic moieties. Herein, we have highlighted the latest status of the responsive nanocarrier drug delivery system, its applications for on–demand delivery of drug candidates for ulcerative colitis, and the prospects are underpinned.

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Metformin-Loaded Alginate Nanoparticles Inhibits Mouse Atherosclerosis by Regulating Macrophage Differentiation by Activating the Adenosine Monophosphate-Activated Protein Kinase/Signal Transducer and Activator of Transcription 3 Pathway

Yang

Zhou

Wang

et al. 2022

j biomed nanotechnol

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Objective: By modulating macrophage phenotype and the adenylate-activated protein kinase/signal transducer and activator of transcription 3 (STAT3) signaling pathway, metformin-loaded alginate nanoparticles may prevent atherosclerosis (As). Methods: Flow cytometry was used to determine the percentage of macrophages with distinct phenotypes (CD86 and CD206). Analysis of protein expression levels of iNOS, arginase 1, AMPK, pAMPK, STAT3 and phosphorylated STAT3 were performed by Western Blot. To confirm the in vitro findings, ApoE−/− mice were employed. Results: AMPK activity and the fraction of M2 macrophages dramatically increased in cells treated with Met, but STAT3 activity was considerably reduced. It was also shown that the Met group had much shorter aortas and lower levels of lipid deposition than that of the control group; also, the fraction of M1 macrophages in the lipid plaques of the animals treated with Met was dramatically reduced by using immunofluorescence labeling. There was a considerable increase in AMPK activity in the Met group, but STAT3 activity was dramatically lowered. Conclusion: According to the results of this study, STAT3 activity is regulated by activation of AMPK and macrophage development in plaques is prevented in mice by metformin-loaded alginate nanoparticles.

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Reactive Oxygen Species-Responsive Polyether Micelle Nanomaterials for Targeted Treatment of Ulcerative Colitis

Cited by 6 publications

References 37 publications

Integrative analysis revealed the role of glucagon-like peptide-2 in improving experimental colitis in mice by inhibiting inflammatory pathways, regulating glucose metabolism, and modulating gut microbiota

Integrative analysis revealed the role of glucagon-like peptide-2 in improving experimental colitis in mice by inhibiting inflammatory pathways, regulating glucose metabolism, and modulating gut microbiota

Responsive nanosystems for targeted therapy of ulcerative colitis: Current practices and future perspectives

Metformin-Loaded Alginate Nanoparticles Inhibits Mouse Atherosclerosis by Regulating Macrophage Differentiation by Activating the Adenosine Monophosphate-Activated Protein Kinase/Signal Transducer and Activator of Transcription 3 Pathway

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