Zhao Yunchun, Zheng Caihong, Zhang Li, Chen Yue, Ye Yiqing, Zhao Mengdan
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.
Women's Hospital, Medicine of School, Zhejiang University, Hangzhou 310006, China.
Colloids Surf B Biointerfaces. 2015 Mar 1;127:155-63. doi: 10.1016/j.colsurfb.2015.01.034. Epub 2015 Jan 28.
Biodegradable and biocompatible poly(d,l-lactic-co-glycolic acid) (PLGA)was conjugated to the 5'-thiol end of signal transducer and activator of transcription 3 (STAT3) small interfering RNA (STAT3-siRNA) via a disulfide bond. In aqueous environments, these siRNA-PLGA conjugates can spontaneously form core/shell type spherical micelles with a particle size of about 200 nm. A biodegradable, low molecular weight cationic polymer, chitosan oligosaccharide (CSO), was added to the siRNA-PLGA micelles at different nitrogen to phosphate (N/P) ratios to form stable, spherical siRNA-PLGA/CSO micelles with sizes of 150-180 nm. The siRNA-PLGA/CSO micelles were produced via ionic complexation between negatively charged siRNA and positively charged CSO on the outer shell of the micelles. The siRNA-PLGA/CSO micelles exhibited superior cellular uptake and STAT3 gene silencing efficiency in SKOV3 ovarian cancer cells when compared with siRNA/CSO complexes at the same N/P ratios with no significant differences with lipofectamine 2000. Furthermore, the siRNA-PLGA/CSO micelles showed that the efficiencies of cellular uptake and STAT3 gene silencing gradually increased with increasing N/P ratios. The siRNA-PLGA/CSO micelles also inhibited the growth of SKOV3 cells, as well as, promoted apoptosis of the cells. These results indicate that siRNA-PLGA/CSO micelles can be utilized as a novel and efficient siRNA carrier to treat a variety of diseases.
可生物降解且具有生物相容性的聚（d，l-乳酸-共-乙醇酸）（PLGA）通过二硫键与信号转导和转录激活因子3（STAT3）小干扰RNA（STAT3-siRNA）的5'-硫醇末端偶联。在水性环境中，这些siRNA-PLGA偶联物可自发形成粒径约为200 nm的核/壳型球形胶束。将一种可生物降解的低分子量阳离子聚合物壳寡糖（CSO）以不同的氮磷比（N/P）添加到siRNA-PLGA胶束中，以形成尺寸为150-180 nm的稳定球形siRNA-PLGA/CSO胶束。siRNA-PLGA/CSO胶束是通过胶束外壳上带负电荷的siRNA与带正电荷的CSO之间的离子络合产生的。与相同N/P比的siRNA/CSO复合物相比，siRNA-PLGA/CSO胶束在SKOV3卵巢癌细胞中表现出优异的细胞摄取和STAT3基因沉默效率，与脂质体2000无显著差异。此外，siRNA-PLGA/CSO胶束表明，细胞摄取效率和STAT3基因沉默效率随N/P比的增加而逐渐提高。siRNA-PLGA/CSO胶束还抑制了SKOV3细胞的生长，并促进了细胞凋亡。这些结果表明，siRNA-PLGA/CSO胶束可作为一种新型高效的siRNA载体用于治疗多种疾病。
