Dismantling the Necroptotic Engine: An Oral Theranostic Nanosponge for Ulcerative Colitis

Yao Xiao; Xu Chen; Jingnan Liao; Jinjin Wang; Lili Lu; Huan Chen; Chengu Niu; Mingyuan Wang

doi:10.1002/adma.202516297

journal article·2026-05

Dismantling the Necroptotic Engine: An Oral Theranostic Nanosponge for Ulcerative Colitis

Yao Xiao, Xu Chen, Jingnan Liao, Jinjin Wang, Lili Lu, Huan Chen, Chengu Niu, Mingyuan Wang

Advanced Materials· Volume 38· Issue 27

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Source abstract

Abstract

ABSTRACT Ulcerative Colitis (UC) treatments often lack target specificity and have significant side effects. A key pathological driver is the excessive necroptosis of intestinal epithelial cells (IECs), which disrupts the gut barrier. To address this, we designed an intelligent oral theranostic nanoplatform, CurN@I, to dismantle the necroptosis‐inflammation axis. CurN@I consists of a barium sulfate (BaSO ₄ ) core for computed tomography (CT) imaging, encapsulated within a pH‐responsive silk protein nanosponge. This scaffold is co‐loaded with a necroptosis inhibitor (Necrostatin‐1s, Nec‐1s) and an antioxidant (demethoxycurcumin, DMC). The nanostructure is condensed in the acidic stomach but swells at the neutral pH of the inflamed intestine for localized drug release. Its negative surface charge facilitates durable electrostatic adhesion to the inflamed mucosa. In murine UC models, oral CurN@I significantly outperformed first‐line clinical drugs. Mechanistic analysis showed it inhibits IEC necroptosis, alleviates oxidative stress, promotes barrier regeneration, and reshapes the gut microbiome. This work presents a non‐invasive, targeted oral strategy that integrates diagnosis with multi‐faceted therapy to restore intestinal homeostasis, demonstrating strong potential for clinical translation.

Source: crossref · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: Cell death mechanisms and regulation · Inflammatory Bowel Disease · Curcumin's Biomedical Applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Geriatric Surgery Xiangya Hospital Central South University Changsha China

National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University Changsha China

Department of General Surgery Xiangya Hospital Central South University Changsha China

International Joint Research Center of Minimally Invasive Endoscopic Technology Equipment and Standards Xiangya Hospital Central South University Changsha China

Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control Changsha Hospital For Maternal and Child Health Care Affiliated to Hunan Normal University Changsha China

Central laboratory the Affiliated Zhuzhou Hospital Xiangya Medical College Central South University Zhuzhou China

Institute of Digestive Diseases Longhua Hospital Shanghai University of Traditional Chinese Medicine Shanghai China

State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine Shanghai China

School of Public Health Shanghai University of Traditional Chinese Medicine Shanghai China

Gastroenterology/Hepatology University of Nebraska Medical Center Omaha NE USA

Funding

National Natural Science Foundation of China

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