Treatment of Ulcerative Colitis by Cationic Liposome Delivered NLRP3 siRNA

作者：Jing Huang, Mengmeng Dai, Mingxia He, Weicheng Bu, Liwen Cao, Jing Jing, Run Cao, Hailong Zhang, Ke Men · 发表于：International Journal of Nanomedicine · 年份：2023 · DOI：10.2147/ijn.s413149 · 被引用次数：21 · 研究领域：Inflammasome and immune disorders、Autoimmune and Inflammatory Disorders Research

Purpose: 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 cells. Finally, we assessed the safety of CLP/siNLRP3. Results: The prepared CLP was spherical, with a small particle size (94 nm) and low permeability. The CLP could efficiently protect siNLRP3 from degradation and then deliver siNLRP3 into PMs, inhibiting NLRP3 inflammasome activation. Also, the CLP/siNLRP3 could inhibit the secretion of mature IL-1β and IL-18 from PMs, thereby achieving a favorable anti-inflammation effect. In vivo, CLP/siNLRP3 coul...