The 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.
Department of Pharmacology & the Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
Int J Nanomedicine. 2021 Jan 13;16:345-357. doi: 10.2147/IJN.S286392. eCollection 2021.
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).
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.
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.
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.
我们之前的研究发现，缺失分选连接蛋白 10（SNX10）可以预防葡聚糖硫酸钠（DSS）诱导的结肠炎症和病理损伤。这启发我们，调节结肠上皮细胞中的 SNX10 表达可能代表一种有前途的炎症性肠病（IBD）治疗策略。
有效递送 siRNA/shRNA 以沉默基因是治疗多种疾病的高度追求手段。在这里，我们将 SNX10-shRNA 质粒（SRP）包封在聚乳酸-聚乙二醇（PLGA）中制成口服纳米颗粒（NPs），然后分别应用于急性和慢性 IBD 小鼠模型。检测了纳米颗粒的特性，并评估了 SRP-NPs 对小鼠 IBD 的影响。
成功构建了高效的 SNX10-shRNA 质粒，并涂覆 PLGA 以获得粒径为 275.2±11.4mm、均匀的 PDI 分布、包封效率为 87.6±2.5%、载药量为 13.11±1.38%的纳米颗粒，在结肠中显示出 SNX10 RNA 干扰的优势效率。在急性和慢性 IBD 模型中，SRP-NPs 能够有效减轻小鼠体重减轻，缓解肠黏膜损伤和炎症浸润，抑制炎症细胞因子 IL-1β、IL-23、TNF-α 的表达，并下调 Toll 样受体（TLRs）2 和 4 的表达。
SNX10-shRNA 质粒口服纳米颗粒在结肠中显示出 SNX10 RNA 干扰的优势效率，并通过 TLR 信号通路改善小鼠结肠炎。SNX10 是治疗 IBD 的新靶点，SNX10-shRNA 质粒纳米颗粒可能是治疗 IBD 的一种有前途的治疗选择。
