Dataset Information

Oral enzyme-responsive nanoprobes for targeted theranostics of inflammatory bowel disease.

ABSTRACT:

Background

Inflammatory bowel disease (IBD) is a progressive and debilitating inflammatory disease of the gastrointestinal tract (GIT). Despite recent advances, precise treatment and noninvasive monitoring remain challenging.

Methods

Herein, we developed orally-administered, colitis-targeting and hyaluronic acid (HA)-modified, core-shell curcumin (Cur)- and cerium oxide (CeO₂)-loaded nanoprobes (Cur@PC-HA/CeO₂ NPs) for computed tomography (CT) imaging-guided treatment and monitoring of IBD in living mice.

Results

Following oral administration, high-molecular-weight HA maintains integrity with little absorption in the upper GIT, and then actively accumulates at local colitis sites owing to its colitis-targeting ability, leading to specific CT enhancement lasting for 24 h. The retained NPs are further degraded by hyaluronidase in the colon to release Cur and CeO₂, thereby exerting anti-inflammatory and antioxidant effects. Combined with the ability of NPs to regulate intestinal flora, the oral NPs result in substantial relief in symptoms. Following multiple treatments, the gradually decreasing range of the colon with high CT attenuation correlates with the change in the clinical biomarkers, indicating the feasibility of treatment response and remission.

Conclusion

This study provides a proof-of-concept for the design of a novel theranostic integration strategy for concomitant IBD treatment and the real-time monitoring of treatment responses.

SUBMITTER: Cao L

PROVIDER: S-EPMC11321179 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

Oral enzyme-responsive nanoprobes for targeted theranostics of inflammatory bowel disease.

Cao Lin L Duan Dengyi D Peng Jing J Li Ruinan R Cao Qi Q Li Xinwen X Guo Yunfei Y Li Jianmin J Liu Kangkang K Li Yiming Y Zhang Wenyi W Liu Shuang S Zhang Xuening X Zhao Yang Y

Journal of nanobiotechnology 20240813 1

<h4>Background</h4>Inflammatory bowel disease (IBD) is a progressive and debilitating inflammatory disease of the gastrointestinal tract (GIT). Despite recent advances, precise treatment and noninvasive monitoring remain challenging.<h4>Methods</h4>Herein, we developed orally-administered, colitis-targeting and hyaluronic acid (HA)-modified, core-shell curcumin (Cur)- and cerium oxide (CeO<sub>2</sub>)-loaded nanoprobes (Cur@PC-HA/CeO<sub>2</sub> NPs) for computed tomography (CT) imaging-guided ...[more]

PMID: 39138477

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Project description:To improve quality of life and prevent long-term risks in patients with inflammatory bowel diseases (IBDs: Crohn's disease, ulcerative colitis), it is essential to suppress inflammatory activity adequately. However, corticosteroids are only suitable for therapy of acute flares and the evidence for positive effects of immunosuppressive substances like azathioprine or 6-mercapropurine is mainly limited to maintenance of remission. In addition, only subgroups of patients benefit from biologicals targeting tumour necrosis factor α or α4β7 integrins. In summary, until now the disease activity is not sufficiently controlled in a relevant fraction of the patients with IBD. Thus, there is an urge for the development of new substances in the therapy of ulcerative colitis and Crohn's disease. Fortunately, new oral and parenteral substances are in the pipeline. This review will focus on oral substances, which have already passed phase II studies successfully at this stage. In this article, we summarize data regarding AJM300, phosphatidylcholine (LT-02), mongersen, ozanimod, filgotinib and tofacitinib. AJM300 and ozanimod were tested in patients with ulcerative colitis and target lymphocyte trafficking through inhibition of the α subunit of integrin, respectively binding to the sphingosine-1-phosphate receptor (subtypes 1 and 5) on lymphocytes. Mongersen was utilized in patients with Crohn's disease and accelerates the degradation of SMAD7 mRNA, which consequently strengthens the mainly anti-inflammatory signalling pathway of transforming growth factor β1. Various Janus kinase (JAK) inhibitors were developed, which inhibit the intracellular signalling pathway of cytokines. For example, the JAK1 blocker filgotinib was tested in Crohn's disease, whereas the JAK1/3 inhibitor tofacitinib was tested in clinical trials for both Crohn's disease and ulcerative colitis. A different therapeutic approach is the substitution of phosphatidylcholine (LT-02), which might recover the colonic mucus. Taken together, clinical trials with these new agents have opened avenues for further clinical studies and it can be expected that at least some of these agents will be finally approved for clinical therapy.

Dataset Information

Oral enzyme-responsive nanoprobes for targeted theranostics of inflammatory bowel disease.

Background

Methods

Results

Conclusion

Publications

Oral enzyme-responsive nanoprobes for targeted theranostics of inflammatory bowel disease.

Similar Datasets

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