Vascular Endothelial Growth Factor-C siRNA Delivered via Calcium Carbonate Nanoparticle Effectively Inhibits Lymphangiogenesis and Growth of Colorectal Cancer In Vivo
Vascular Endothelial Growth Factor-C siRNA Delivered via Calcium Carbonate Nanoparticle Effectively Inhibits Lymphangiogenesis and Growth of Colorectal Cancer In Vivo
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通过碳酸钙纳米颗粒传递的血管内皮生长因子-C siRNA 可有效抑制体内淋巴管生成和结直肠癌生长
DOI：
10.1089/cbr.2008.0515
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发表时间：
2009-04-01
影响因子：
3.4
通讯作者：
Zhang, Liyuan
中科院分区：
文献类型：
--
作者：
He, Xiao-Wen;Liu, Ting;Zhang, Liyuan
评估了非病毒基因载体碳酸钙 (CaCO3) 纳米颗粒在体外和体内有效递送 siRNA 靶向血管内皮生长因子 -C (VEGF-C) 的能力。化学合成的 CaCO3 纳米颗粒直径为 58 nm，表面带正电荷 + 28.6 mV。它能够形成CaCO3-纳米粒子-DNA复合物，并以高转染效率将DNA转移到靶细胞中，同时有效保护封装的DNA不被降解。此外，CaCO3-纳米粒子-DNA复合物对LoVo细胞没有明显的细胞毒性，而脂质体-DNA复合物表现出可测量的细胞毒性。通过实时聚合酶链式反应 (PCR) 和酶联免疫吸附测定检测，通过 CaCO3 纳米颗粒转染 VEGF-C 靶向小干扰 RNA (siRNA) 的 LoVo 细胞表现出 VEGF-C 表达显着降低，而在对照转染处理的细胞中未观察到 VEGF-C 表达降低。通过 CaCO3 纳米颗粒用 VEGF-C siRNA 转染 LoVo 细胞还可以显着抑制皮下异种移植物中的肿瘤淋巴管生成、肿瘤生长和区域淋巴结转移。实时 PCR 证实，与对照相比，经 VEGF-C siRNA 处理的 LoVo 细胞皮下异种移植物中 VEGF-C 信使 RNA 表达显着下调。我们得出的结论是，CaCO3(-)纳米颗粒是一种新型的非病毒系统，可有效递送 siRNA 以进行癌症基因治疗。
A nonviral gene carrier, calcium carbonate (CaCO3)-nanoparticle, was evaluated for the efficient in vitro and in vivo delivery of siRNA-targeting vascular endothelial growth factor-C (VEGF-C). The chemically synthesized CaCO3-nanoparticle has a 58-nm diameter and a + 28.6-mV positive surface charge. It is capable of forming a CaCO3-nanoparticle-DNA complex and transferring DNA into targeted cells with high transfection efficiency, while effectively protecting the encapsulated DNA from degradation. Further, the CaCO3-nanoparticle-DNA complex has no obvious cytotoxicity for LoVo cells, while a liposome-DNA complex exhibited measurable cytotoxicity. LoVo cells transfected with a VEGF-C-targeted small interfering RNA (siRNA) via the CaCO3-nanoparticle exhibits significantly reduced VEGF-C expression, as measured by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay, whereas no decrease in VEGF-C expression is observed in cells treated by control transfection. Transfection of LoVo cells with VEGF-C siRNA via the CaCO3-nanoparticle also dramatically suppresses tumor lymphangiogenesis, tumor growth, and regional lymph-node metastasis in subcutaneous xenografts. Significant downregulation of VEGF-C messenger RNA expression in a subcutaneous xenograft derived from VEGF-C siRNA-treated LoVo cells was confirmed by real-time PCR, as compared to controls. We conclude that the CaCO3(-)nanoparticle is a novel, nonviral system for the effective delivery of siRNA for cancer gene therapy.