Treatment of Ulcerative Colitis by Cationic Liposome Delivered NLRP3 siRNA

Jing Huang,1,* Mengmeng Dai,1,* Mingxia He,1,* Weicheng Bu,1 Liwen Cao,1 Jing Jing,1 Run Cao,1 Hailong Zhang,1 Ke Men2 1Joint National Laboratory for Antibody Drug Engineering, The First Affiliated Hospital, Henan University, Kaifeng, Henan Province, 475004, People’s Republic of China; 2State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, 610044, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hailong Zhang, Joint National Laboratory for Antibody Drug Engineering, The First Affiliated Hospital, Henan University, Kaifeng, Henan Province, 475004, People’s Republic of China, Email hailong6891@163.com Ke Men, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, 610044, People’s Republic of China, Email mendingbob@hotmail.comPurpose: The abnormal activation of NLRP3 inflammasome is related to the occurrence and development of ulcerative colitis (UC). However, the ideal drug and delivery system remain important factors limiting the targeting of NLRP3 inflammasome in UC therapy. Gene therapy by delivering siRNA is effective in treating various diseases. Therefore, delivering siNLRP3 using an ideal vector for UC treatment is necessary.Materials and Methods: Nanoparticles delivering siNLRP3 were developed based on cationic liposome (CLP/siNLRP3). Their ability to inhibit NLRP3 inflammasome activation was monitored using Western blot (WB) and Enzyme-linked Immunosorbent Assay (ELISA). The ASC oligomerization in LPS-primed peritoneal macrophages (PMs) was detected by WB and immunofluorescence. Moreover, we assessed the role of CLP/siNLRP3 on dextran sodium sulfate (DSS)-induced UC by examining NLRP3 levels, pro-inflammatory cytokines expression, and disease-associated index (DAI). Flow cytometry (FCM) was used to detect the contents of macrophages and T cell