Receptor-targeted nanoparticles for in vivo imaging of breast cancer.
Receptor-targeted nanoparticles for in vivo imaging of breast cancer.
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DOI：
10.1158/1078-0432.ccr-08-3289
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发表时间：
2009-07-15
期刊：
影响因子：
--
通讯作者：
Mao H
中科院分区：
文献类型：
--
作者：
Yang L;Peng XH;Wang YA;Wang X;Cao Z;Ni C;Karna P;Zhang X;Wood WC;Gao X;Nie S;Mao H
细胞表面受体靶向的磁性氧化铁 (IO) 纳米粒子提供分子磁共振成像 (MRI) 造影剂，用于提高人类癌症检测的特异性。本研究报告了一种新型靶向 IO 纳米颗粒的开发，该纳米颗粒使用含有与 IO 纳米颗粒缀合的尿激酶纤溶酶原激活剂氨基末端片段 (ATF) 的重组肽 (ATF-IO)。这种纳米颗粒靶向尿激酶纤溶酶原激活剂受体（uPAR），该受体在乳腺癌组织中过度表达。 ATF-IO 纳米颗粒能够特异性结合表达 uPAR 的肿瘤细胞并被其内化。将 ATF-IO 纳米粒子全身递送到患有皮下和腹膜内乳腺肿瘤的小鼠中，导致粒子在肿瘤中积聚，产生可通过临床 MRI 扫描仪在 3 特斯拉场强下检测到的强 MRI 对比度。使用与 IO 纳米颗粒缀合的近红外 (NIR) 染料标记的 ATF 肽对乳腺肿瘤进行近红外 (NIR) 荧光成像，进一步证实了体内 MRI 证明的 ATF-IO 纳米颗粒的靶特异性。此外，与接受非靶向IO纳米颗粒的小鼠相比，施用ATF-IO纳米颗粒的小鼠在肝脏和脾脏中表现出较低的颗粒摄取。我们的结果表明，uPAR 靶向 ATF-IO 纳米颗粒具有作为分子靶向、双模态成像剂用于乳腺癌体内成像的潜力。
Cell surface receptor-targeted magnetic iron oxide (IO) nanoparticles provide molecular magnetic resonance imaging (MRI) contrast agents for improving specificity of the detection of human cancer. The present study reports the development of a novel targeted IO nanoparticle using a recombinant peptide containing the amino-terminal fragment (ATF) of urokinase plasminogen activator conjugated to IO nanoparticles (ATF-IO). This nanoparticle targets urokinase plasminogen activator receptor (uPAR), which is overexpressed in breast cancer tissues. ATF-IO nanoparticles are able to specifically bind to and be internalized by uPAR-expressing tumor cells. Systemic delivery of ATF-IO nanoparticles into mice bearing subcutaneous and intraperitoneal mammary tumors leads to the accumulation of the particles in tumors, generating a strong MRI contrast detectable by a clinical MRI scanner at a field strength of 3 Tesla. Target specificity of ATF-IO nanoparticles demonstrated by in vivo MRI is further confirmed by near infrared (NIR) fluorescence imaging of the mammary tumors using NIR dye-labeled ATF peptides conjugated to IO nanoparticles. Furthermore, mice administered ATF-IO nanoparticles exhibit lower uptake of the particles in the liver and spleen compared to those receiving non-targeted IO nanoparticles. Our results suggest that uPAR-targeted ATF-IO nanoparticles have potential as molecularly-targeted, dual modality imaging agents for in vivo imaging of breast cancer.