2. Academic Validation
  3. Dismantling the Necroptotic Engine: An Oral Theranostic Nanosponge for Ulcerative Colitis

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

  • Adv Mater. 2026 Jan 16:e16297. doi: 10.1002/adma.202516297.
Yao Xiao 1 2 3 4,  Xu Chen 1 2 3 4,  Jingnan Liao 5,  Jinjin Wang 6,  Lili Lu 7 8 9,  Huan Chen 6,  Chengu Niu 10,  Mingyuan Wang 1 2 3 4
Affiliations

Affiliations

  • 1 Department of Geriatric Surgery, Xiangya Hospital, Central South University, Changsha, China.
  • 2 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
  • 3 Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China.
  • 4 International Joint Research Center of Minimally Invasive Endoscopic Technology Equipment and Standards, Xiangya Hospital, Central South University, Changsha, China.
  • 5 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.
  • 6 Central laboratory, the Affiliated Zhuzhou Hospital Xiangya Medical College, Central South University, Zhuzhou, China.
  • 7 Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • 8 State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine, Shanghai, China.
  • 9 School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • 10 Gastroenterology/Hepatology, University of Nebraska Medical Center, Omaha, NE, USA.
PMID: 41546396 DOI: 10.1002/adma.202516297
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 (BaSO4) 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.

Keywords

CurN@I; intestinal epithelial cells; necroptosis; theranostics; ulcerative colitis.

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