Nanoparticle imaging of integrins on tumor cells
Nanoparticle imaging of integrins on tumor cells
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DOI：
10.1593/neo.05769
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发表时间：
2006-03-01
期刊：
影响因子：
4.8
通讯作者：
Josephson, Lee
中科院分区：
文献类型：
--
作者：
Montet, Xavier;Montet-Abou, Karin;Josephson, Lee
粒径在10到100纳米之间的纳米颗粒可以向分子靶标输送大量的有效载荷，但通过输送屏障的扩散和/或运输速度很慢。为了验证纳米颗粒靶向肿瘤细胞中表达的标记物的可行性，我们使用环精氨酸-甘氨酸-天冬氨酸（RGD）纳米颗粒靶向整合素在BT-20肿瘤上的结合作为模型系统。本研究的目的是：1)利用纳米颗粒对BT-20肿瘤细胞中表达的α V β(3)整合素进行荧光成像和磁共振成像；2)确定与纳米颗粒靶向肿瘤细胞整合素能力相关的因素。1)肿瘤细胞整合素表达（α v β(3)整合素在BT-20细胞中表达，而在9L细胞中不表达）；2)纳米颗粒药代动力学（循环RGD肽交联氧化铁的血液半衰期为180分钟，在较长的循环时间内能够从血管中逃逸）；3)肿瘤血管化（肿瘤有致密的毛细血管床，毛细血管之间的距离< 100 μ m）。这些结果表明，至少在纳米颗粒和肿瘤模型具有与本文采用的BT-20肿瘤相似的特征的情况下，纳米颗粒可以靶向肿瘤细胞中表达的细胞表面标记物。
Nanoparticles 10 to 100 nm in size can deliver large payloads to molecular targets, but undergo slow diffusion and/or slow transport through delivery barriers. To examine the feasibility of nanoparticles targeting a marker expressed in tumor cells, we used the binding of cyclic arginine-glycine-aspartic acid (RGD) nanoparticle targeting integrins on BT-20 tumor as a model system. The goals of this study were: 1) to use nanoparticles to image alpha V beta(3) integrins expressed in BT-20 tumor cells by fluorescence-based imaging and magnetic resonance imaging, and, 2) to identify factors associated with the ability of nanoparticles to target tumor cell integrins. Three factors were identified: 1) tumor cell integrin expression ( the alpha v beta(3) integrin was expressed in BT-20 cells, but not in 9L cells); 2) nanoparticle pharmacokinetics ( the cyclic RGD peptide cross-linked iron oxide had a blood half-life of 180 minutes and was able to escape from the vasculature over its long circulation time); and 3) tumor vascularization ( the tumor had a dense capillary bed, with distances of < 100 mu m between capillaries). These results suggest that nanoparticles could be targeted to the cell surface markers expressed in tumor cells, at least in the case wherein the nanoparticles and the tumor model have characteristics similar to those of the BT-20 tumor employed here.