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首页> 外文期刊>International Journal of Nanomedicine >Development of small interfering RNA delivery system using PEI-PEG-APRPG polymer for antiangiogenic vascular endothelial growth factor tumor-targeted therapy
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Development of small interfering RNA delivery system using PEI-PEG-APRPG polymer for antiangiogenic vascular endothelial growth factor tumor-targeted therapy

机译：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

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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.
机译：背景：小分子干扰RNA（siRNA）可使细胞质中的靶基因沉默，并成为基因治疗的主要工具。血管内皮生长因子（VEGF）是血管生成的有效调节剂，在大多数肿瘤中均过表达，并且与肿瘤的生长和转移密切相关。研究表明，siRNA抑制VEGF表达是一种有效的抗血管生成肿瘤治疗方法。方法：在本研究中，我们合成了PEI-PEG-APRPG靶向递送系统，并结合了血管生成的归巢Ala-Pro-通过亲水性聚乙二醇（PEG）间隔基将Arg-Pro-Gly（APRPG）肽转变为阳离子聚乙烯亚胺（PEI）。结果：PEI-PEG-APRPG有效地将siRNA冷凝成20–50 nm纳米颗粒，表面带有正电荷合适的N / P比。 siRNA / PEI-PEG-APRPG复合物有效增强了siRNA在RNase A中的稳定性，并提高了siRNA在体外的增殖抑制能力和转染效率以及体内肿瘤的积累。此外，siRNA / PEI-PEG-APRPG复合物在肿瘤生长，微血管密度以及VEGF蛋白和mRNA水平方面具有很高的抗肿瘤治疗效果。结论：这些发现表明PEI-PEG-APRPG有效地将siRNA传递至肿瘤。过表达VEGF，从而抑制肿瘤生长。

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