In vivo angiogenesis imaging of solid tumors by αvβ3-targeted, dual-modality micellar nanoprobes
In vivo angiogenesis imaging of solid tumors by αvβ3-targeted, dual-modality micellar nanoprobes
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DOI：
10.1258/ebm.2010.010096
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发表时间：
2010-08-01
影响因子：
3.2
通讯作者：
Gao, Jinming
中科院分区：
文献类型：
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作者：
Kessinger, Chase W.;Khemtong, Chalermchai;Gao, Jinming
本研究的目的是开发和评估一种由荧光超顺磁性聚合物胶束 (FSPPM) 组成的 α(v)β(3) 特异性纳米探针，用于肿瘤血管生成的体内成像。使用与四甲基罗丹明（一种荧光染料）缀合的聚（乙二醇）-b-聚（D3L-丙交酯）共聚物生产球形胶束，并负载超顺磁性氧化铁纳米颗粒。通过动态光散射和透射电子显微镜测量，所得胶束直径为50-70 nm。胶束由 α(v)β(3) 特异性肽、环状 RGDfK 编码，并针对体外 α(v)β(3) 过表达细胞中的最大荧光和靶向进行了优化。在小鼠中，cRGD-FSPPM 处理的动物在人肺癌皮下肿瘤异种移植物中显示出 alpha(v)beta(3) 特异性 FSPPM 积累。与组织学验证一起，三维梯度回波磁共振成像 (MRI) 数据使用靶向超灵敏 MRI 纳米探针，提供动物肿瘤模型中血管生成脉管系统的高空间分辨率绘图和量化。
The objective of this study was to develop and evaluate an alpha(v)beta(3)-specific nanoprobe consisting of fluorescent superparamagnetic polymeric micelles (FSPPM) for in vivo imaging of tumor angiogenesis. Spherical micelles were produced using poly(ethylene glycol)-b-poly(D3L-lactide) co-polymers conjugated with tetramethylrhodamine, a fluorescent dye, and loaded with superparamagnetic iron oxide nanoparticles. The resulting micelle diameter was 50-70 nm by dynamic light scattering and transmission electron microscopy measurements. Micelles were encoded with an alpha(v)beta(3)-specific peptide, cyclic RGDfK, and optimized for maximum fluorescence and targeting in alpha(v)beta(3)-overexpressing cells in vitro. In mice, cRGD-FSPPM-treated animals showed alpha(v)beta(3)-specific FSPPM accumulation in human lung cancer subcutaneous tumor xenografts. Together with the histological validation, the three-dimensional gradient echo magnetic resonance imaging (MRI) data provide high spatial resolution mapping and quantification of angiogenic vasculature in an animal tumor model using targeted, ultrasensitive MRI nanoprobes.