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Wei-Lian Bao,1,2,* Qibiao Wu,3,* Bin Hu,2 Dongdong Sun,1 Shengnan Zhao,1 Xiaoyan Shen,2 Haibo Cheng,1 Weixing Shen1 1The First Clinical Medical College of Nanjing University of Chinese Medicine, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Jiangsu, Nanjing 210023, People’s Republic of China; 2Department of Pharmacology & the Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China; 3State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau 999078, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weixing Shen; Haibo ChengThe First Clinical Medical College of Nanjing University of Chinese Medicine, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, 138 Xianling Ave, Nanjing, Jiangsu 210023, People’s Republic of ChinaEmail weixingshen@njucm.edu.cn; haibocheng@njucm.edu.cnBackground: Our previous study found that deletion of Sorting nexin 10 (SNX10) can protect against colonic inflammation and pathological damage induced by dextran sulfate sodium (DSS). This inspired us that modulation of SNX10 expression in colonic epithelial cells might represent a promising therapeutic strategy for inflammatory bowel disease (IBD).Methods: Effective delivery of siRNA/shRNA to silence genes is a highly sought-after means in the treatment of multiple diseases. Here, we encapsulated SNX10-shRNA plasmids (SRP) with polylactide-polyglycolide (PLGA) to make oral nanoparticles (NPs), and then applied them to acute and chronic IBD mice model, respectively. The characteristics of the nanoparticles were assayed and the effects of SRP-NPs on mouse IBD were evaluated.Results: High-efficiency SNX10-shRNA plasmids were succes