Tumor regression by targeted gene delivery to the neovasculature
Tumor regression by targeted gene delivery to the neovasculature
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DOI：
10.1126/science.1070200
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发表时间：
2002-06-28
期刊：
影响因子：
56.9
通讯作者：
Cheresh, DA
中科院分区：
文献类型：
--
作者：
Hood, JD;Bednarski, M;Cheresh, DA
通过基因递送影响血管生物学的努力由于缺乏对患病组织中的内皮细胞特异性的靶向载体而受到阻碍。在这里，我们表明，一个阳离子纳米粒子（NP）耦合到整合素α v β 3靶向配体可以提供基因选择性地在荷瘤小鼠的血管生成血管。通过产生与突变Raf基因ATP（mu）-Raf缀合的NP来测试该方法的治疗功效，所述突变Raf基因ATP（mu）-Raf响应于多种生长因子而阻断内皮信号传导和血管生成。将NP全身注射到小鼠中导致肿瘤相关内皮细胞凋亡，最终导致肿瘤细胞凋亡和已建立的原发性和转移性肿瘤的持续消退。
Efforts to influence the biology of blood vessels by gene delivery have been hampered by a lack of targeting vectors specific for endothelial cells in diseased tissues. Here we show that a cationic nanoparticle (NP) coupled to an integrin alphavbeta3-targeting ligand can deliver genes selectively to angiogenic blood vessels in tumor-bearing mice. The therapeutic efficacy of this approach was tested by generating NPs conjugated to a mutant Raf gene, ATP(mu)-Raf, which blocks endothelial signaling and angiogenesis in response to multiple growth factors. Systemic injection of the NP into mice resulted in apoptosis of the tumor-associated endothelium, ultimately leading to tumor cell apoptosis and sustained regression of established primary and metastatic tumors.