Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, PR China.
Biomaterials. 2012 Nov;33(33):8685-94. doi: 10.1016/j.biomaterials.2012.08.022. Epub 2012 Aug 24.
A small interfering RNA (siRNA) plasmid DNA (pYr-1.1-hU6-EGFP-siVEGF) was constructed and used for suppressing vascular endothelial growth factor (VEGF) expression and inhibiting tumor growth. Then, a (tyrosyl-seryl-leucine)-polyethyleneimine-poly(ethylene glycol) (YSL-PEI-PEG) conjugate was designed and synthesized as a gene carrier for the delivery of pYr-1.1-hU6-EGFP-siVEGF plasmid. The therapeutic peptide YSL was conjugated to PEI to improve the anti-cancer efficiency, and the PEG chain was introduced to reduce the serum protein adsorption and improve the stability of the complex in the systemic circulation. It was found that YSL-PEI-PEG could efficiently condense plasmid DNA when the vector/DNA weight ratio was higher than 2. Compared with PEI 25 kDa, YSL-PEI-PEG exhibited higher transfection efficiency and lower cytotoxicity. More importantly, the results showed that the gene delivery system owned strong ability to inhibit cancer cell proliferation in vitro and tumor growth in vivo. YSL-PEI-PEG has great potential as a gene vector for clinical applications.
构建了一种小干扰 RNA(siRNA)质粒 DNA(pYr-1.1-hU6-EGFP-siVEGF)，用于抑制血管内皮生长因子(VEGF)的表达并抑制肿瘤生长。然后，设计并合成了一种(酪氨酸-丝氨酸-亮氨酸)-聚亚乙基亚胺-聚乙二醇(YSL-PEI-PEG)缀合物作为 pYr-1.1-hU6-EGFP-siVEGF 质粒的基因载体。治疗性肽 YSL 与 PEI 缀合以提高抗癌效率，并且引入 PEG 链以减少血清蛋白吸附并提高复杂体系在全身循环中的稳定性。研究发现，当载体/DNA 重量比高于 2 时，YSL-PEI-PEG 可以有效地浓缩质粒 DNA。与 25 kDa 的 PEI 相比，YSL-PEI-PEG 表现出更高的转染效率和更低的细胞毒性。更重要的是，结果表明该基因传递系统具有很强的体外抑制癌细胞增殖和体内肿瘤生长的能力。YSL-PEI-PEG 作为基因载体具有很大的临床应用潜力。
