达沙替尼
内部收益率1
干扰素调节因子
方位(导航)
化学
二硫键
干扰素
IRF5公司
细胞生物学
癌症研究
转录因子
免疫学
医学
信号转导
生物化学
生物
酪氨酸激酶
基因
地图学
地理
作者
Hamed Vakilzadeh,Jaleh Varshosaz,Mohammad Dinari,Mina Mirian,Sahel Soghrati
标识
DOI:10.1016/j.ijbiomac.2024.137094
摘要
Co-delivery of chemical drugs and nucleic acids has attracted a great interest recently for treatment of inflammatory diseases. Dasatinib (DB), a tyrosine kinase inhibitor with anti-cancer effects, and Interferon Regulatory Factor 5 (IRF5) siRNA have shown anti-inflammatory effects. In the present study, a novel redox-responsive polymeric micelle was designed for co-delivery of DB and IRF5 siRNA-expressing plasmid (psiRF5) to enhance anti-inflammatory effects on macrophages. psiRF5 was condensed efficiently to redox-responsive micelles of DB-conjugated chitosan (CN) composed of disulfide bond, from different molecular weights of CN to form CN-SS-DB/psiRF5 micelles. The micelles with optimum N/P ratios had particle sizes of 287.8 and 245.4 nm and positive zeta potentials. The disulfide bond bearing micelles showed a redox-responsive drug release, protected the plasmid from being dissociated or degraded in exposure with heparin, serum and DNase I, and significantly enhanced the transfection efficiency and IRF5-gene silencing compared to naked psiRF5. The optimum micelles exhibited a dramatic reduction in IRF5 expression and revealed a notably higher anti-inflammatory effect than either DB or psiRF5, as indicated by more IL-10 and less IL-6 and TNF-α production by LPS-stimulated RAW264.7 macrophages incubated with the co-delivery system. The resultant nanocarriers might be promising for more effective treatment of inflammatory diseases.
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