Targeting tumor angiogenic vasculature using polymer-RGD conjugates
Targeting tumor angiogenic vasculature using polymer-RGD conjugates
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DOI：
10.1016/j.jconrel.2004.09.023
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发表时间：
2005-01-20
影响因子：
10.8
通讯作者：
Line, BR
中科院分区：
文献类型：
--
作者：
Mitra, A;Mulholland, J;Line, BR
新血管生成的位点是重要的化疗靶点。本研究报道了一种99 m锝标记的水溶性N-（2-羟丙基）甲基丙烯酰胺（HPMA）共聚物的合成、表征、体内成像和生物分布，该共聚物具有双环化Arg-Gly-Asp基序（HPMA共聚物-RGD 4C缀合物）。体外内皮细胞粘附试验表明，HPMA共聚物-RGD 4C缀合物抑制α（v）β（3）介导的内皮细胞粘附，而HPMA共聚物Arg-Gly-Glu对照缀合物（HPMA共聚物-RGE 4C缀合物）和水解的HPMA共聚物前体（HPMA共聚物）显示无活性。静脉内注射后24小时获得的携带前列腺肿瘤的SCID小鼠的免疫组织化学图像表明HPMA共聚物-RGD 4C缀合物比对照HPMA共聚物-RGE 4C缀合物更大的肿瘤定位。24小时尸检放射性数据显示HPMA共聚物-RGD 4C缀合物具有显著较高的（p
Sites of neovascular angiogenesis are important chemotherapy targets. In this study, the synthesis, characterization, in-vivo imaging and biodistribution of a technetium-99m labeled, water-soluble, N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer carrying doubly cyclized Arg-Gly-Asp motifs (HPMA copolymer-RGD4C conjugate) are reported. In vitro endothelial cell adhesion assays indicated that HPMA copolymer-RGD4C conjugates inhibited alpha(v)beta(3)-mediated endothelial cell adhesion while HPMA copolymer Arg-Gly-Glu control conjugates (HPMA copolymer-RGE4C conjugate) and hydrolyzed HPMA copolymer precursor (HPMA copolymer) showed no activity. The scintigraphic images of prostate tumor bearing SCID mice obtained 24 h post-i.v. injection indicated greater tumor localization of HPMA copolymer-RGD4C conjugate than the control, HPMA copolymer-RGE4C conjugate. The 24-h necropsy radioactivity data showed that HPMA copolymer-RGD4C conjugate had significantly higher (p