College of Pharmacy & Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, Republic of Korea.
Pharm Res. 2012 Apr;29(4):1007-19. doi: 10.1007/s11095-011-0642-z. Epub 2011 Dec 15.
A poly-L-arginine (PLR) and dextran sulfate (DEX)-based nano-sized polyelectrolyte complex (nanocomplex) was developed for epidermal growth factor receptor (EGFR) siRNA delivery for the treatment of head and neck cancer.
PLR and DEX-based nanocomplex including EGFR siRNA was prepared and characterized. In vitro cellular uptake efficiency and EGFR gene silencing effect of nanocomplex including EGFR siRNA were evaluated in Hep-2 and FaDu cells. Its in vivo anti-tumor efficacy was also assessed in FaDu tumor xenografted mouse model.
The weight ratio of polymer:RNA was 15:1 and a nanocomplex system consisting of <200 nm in mean diameter and a positive surface charge was prepared. According to the results of confocal laser scanning microscopy (CLSM) and flow cytometry analyses, the PLR-DEX complex exhibited the best cellular uptake efficiency of EGFR siRNA in Hep-2 and FaDu cells, which led to the highest EGFR gene silencing efficiency in both cell lines. PLR-DEX/EGFR siRNA complex exhibited efficient tumor growth inhibition and EGFR silencing effect in a tumor xenografted mouse model.
PLR and DEX-based nanocomplex containing EGFR siRNA was successfully developed. The new formulation was effective in EGFR gene silencing and tumor growth inhibition in head and neck cancer cells.
开发了一种基于聚精氨酸（PLR）和硫酸葡聚糖（DEX）的纳米聚电解质复合物（纳米复合物），用于表皮生长因子受体（EGFR）siRNA 的递送来治疗头颈部癌症。
制备并表征了包含 EGFR siRNA 的基于 PLR 和 DEX 的纳米复合物。在 Hep-2 和 FaDu 细胞中评估了包含 EGFR siRNA 的纳米复合物的细胞摄取效率和 EGFR 基因沉默效果。还在 FaDu 肿瘤异种移植小鼠模型中评估了其体内抗肿瘤功效。
聚合物：RNA 的重量比为 15:1，并且制备了平均直径<200nm 且带正表面电荷的纳米复合物系统。根据共聚焦激光扫描显微镜（CLSM）和流式细胞术分析的结果，PLR-DEX 复合物在 Hep-2 和 FaDu 细胞中表现出 EGFR siRNA 的最佳细胞摄取效率，从而在这两种细胞系中均表现出最高的 EGFR 基因沉默效率。PLR-DEX/EGFR siRNA 复合物在肿瘤异种移植小鼠模型中表现出有效的肿瘤生长抑制和 EGFR 沉默作用。
成功开发了包含 EGFR siRNA 的基于 PLR 和 DEX 的纳米复合物。该新制剂可有效沉默 EGFR 基因并抑制头颈部癌细胞的生长。
