Biosilicification-mimicking chiral nanostructures for targeted treatment of inflammatory bowel disease

Miao Xu, Wei Xin, Jiabin Xu, Anya Wang, Shuai Ma, Di Dai, Yidan Wang, Dongmei Yang, Lin Zhao () and Heran Li ()
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Miao Xu: China Medical University
Wei Xin: The First Hospital of China Medical University
Jiabin Xu: China Medical University
Anya Wang: China Medical University
Shuai Ma: China Medical University
Di Dai: The First Hospital of China Medical University
Yidan Wang: China Medical University
Dongmei Yang: China Medical University
Lin Zhao: China Medical University
Heran Li: China Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-22

Abstract: Abstract The cascade reaction of lipopolysaccharides (LPS), cell-free DNA (cfDNA), and reactive oxygen species (ROS), drives the development of inflammatory bowel disease (IBD). Herein, we construct polyethylenimide (PEI)-L/D-tartaric acid (L/D-TA) complexes templated mesoporous organosilica nanoparticles (MON) (PEI-L/D-TA@MON) by mimicking biosilicification under ambient conditions within seconds. The chiral nanomedicines include four functional moieties, wherein PEI electrostatically attracts cfDNA, tetrathulfide bonds reductively react with ROS, silanol groups adsorb LPS, and L/D-TA enables chiral recognition and inflammatory localization. Following oral administration, PEI-L-TA@MON exhibiting preferential conformation stereoscopically matches with mucosa and anchors onto inflammatory intestine for lesion targeting. PEI-L-TA@MON eliminates LPS, ROS, and cfDNA, alleviating oxidative stress, inhibiting inflammatory cascade, and maintaining immune homeostasis to achieve IBD therapy. In addition, the rapid synthesis, low cost, energy-free preparation, negligible toxicity, satisfactory therapeutic effect, and facile conversion on therapeutic modes of PEI-L-TA@MON will bring changes for IBD treatment, providing research values and translational clinical prospects.

Date: 2025
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DOI: 10.1038/s41467-025-57890-8

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