Development of small interfering RNA delivery system using PEI-PEG-APRPG polymer for antiangiogenic vascular endothelial growth factor tumor-targeted therapy.
Development of small interfering RNA delivery system using PEI-PEG-APRPG polymer for antiangiogenic vascular endothelial growth factor tumor-targeted therapy.
复制标题
使用PEI-PEG-APRPG聚合物开发小干扰RNA递送系统用于抗血管生成血管内皮生长因子肿瘤靶向治疗
DOI：
10.2147/ijn.s22293
复制
发表时间：
2011
影响因子：
8
通讯作者：
Qi XR
中科院分区：
文献类型：
--
作者：
Lu ZX;Liu LT;Qi XR
背景小干扰RNA（small interfering RNA，siRNA）可使靶基因在细胞质内沉默，是基因治疗的主要工具。血管内皮生长因子（VEGF）是一种强有力的血管生成调节因子，在大多数肿瘤中过表达，与肿瘤的生长和转移密切相关。已经显示，通过siRNA抑制VEGF表达是抗血管生成肿瘤治疗的有效和有用的方法。方法将血管生成导向肽Ala-Pro-Arg-Pro-Gly（APRPG）通过亲水性聚乙二醇（PEG）间隔基与阳离子聚乙烯亚胺（PEI）结合，制备PEI-PEG-APRPG靶向给药系统。结果PEI-PEG-APRPG以合适的N/P比将siRNA有效地凝聚成20-50 nm的表面带正电荷的纳米颗粒。siRNA/PEI-PEG-APRPG复合物有效地增强了siRNA在RNase A中的稳定性，提高了siRNA的体外增殖抑制能力、转染效率和体内肿瘤蓄积。此外，siRNA/PEI-PEG-APRPG复合物在肿瘤生长、微血管密度和VEGF蛋白和mRNA水平方面表现出高效的抗肿瘤治疗。结论PEI-PEG-APRPG能有效地将siRNA导入VEGF高表达的肿瘤细胞，从而抑制肿瘤生长。
Background Small interfering RNA (siRNA) can silence target genes in the cytoplasm and be a major tool in gene therapy. Vascular endothelial growth factor (VEGF), a potent regulator of angiogenesis, is overexpressed in most tumors and is closely associated with tumor growth and metastasis. It has been shown that inhibition of VEGF expression by siRNA is an effective and useful method for antiangiogenic tumor therapy. Methods In the present study, we synthesized a targeted delivery system of PEI-PEG-APRPG incorporating angiogenic vessel-homing Ala-Pro-Arg-Pro-Gly (APRPG) peptide into cationic polyethylenimine (PEI) via a hydrophilic poly(ethylene glycol) (PEG) spacer. Results PEI-PEG-APRPG effectively condensed siRNA into 20–50 nm nanoparticles with a positive surface charge using a suitable N/P ratio. The siRNA/PEI-PEG-APRPG complex effectively enhanced the stability of siRNA in RNase A, and improved the proliferation-inhibiting ability and transfection efficiency of siRNA in vitro and tumor accumulation in vivo. In addition, the siRNA/PEI-PEG-APRPG complex exhibited high efficiency as antitumor therapy with regard to tumor growth, microvessel density, and VEGF protein and mRNA levels. Conclusion These findings suggest that PEI-PEG-APRPG effectively delivers siRNA to tumors overexpressing VEGF and thereby inhibits tumor growth.