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

口服酶反应纳米探针用于炎症性肠病的靶向治疗诊断

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作者:Lin Cao #, Dengyi Duan #, Jing Peng #, Ruinan Li, Qi Cao, Xinwen Li, Yunfei Guo, Jianmin Li, Kangkang Liu, Yiming Li, Wenyi Zhang, Shuang Liu, Xuening Zhang, Yang Zhao

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.

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.

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.

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