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Oral Nanoparticles of SNX10-shRNA Plasmids Ameliorate Mouse Colitis

Authors Bao WL, Wu Q, Hu B, Sun D, Zhao S, Shen X, Cheng H, Shen W

Received 12 October 2020

Accepted for publication 28 December 2020

Published 13 January 2021 Volume 2021:16 Pages 345—357

DOI https://doi.org/10.2147/IJN.S286392

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Lei Yang


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 work

Correspondence: Weixing Shen; Haibo Cheng
The 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 China
Email weixingshen@njucm.edu.cn; haibocheng@njucm.edu.cn

Background: 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 successfully constructed and coated with PLGA to obtain nanoparticles, with a particle size of 275.2 ± 11.4mm, uniform PDI distribution, entrapment efficiency of 87.6 ± 2.5%, and drug loading of 13.11 ± 1.38%, displayed dominant efficiency of SNX10 RNA interference in the colon. In both acute and chronic IBD models, SRP-NPs could effectively reduce the loss of mice body weight, relieve the intestinal mucosal damage and inflammatory infiltration, inhibit the expression of inflammatory cytokines IL-1β, IL-23, TNF-α, and down-regulate the expression of toll-like receptors (TLRs) 2 and 4.
Conclusion: Oral nanoparticles of SNX10-shRNA plasmid displayed dominant efficiency of SNX10 RNA interference in the colon and ameliorate mouse colitis via TLR signaling pathway. SNX10 is a new target for IBD treatment and nanoparticles of SNX10-shRNA plasmid might be a promising treatment option for IBD.

Keywords: SNX10, IBD, shRNA, SRP-NPs, TLR

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