Imaging Metastasis Using an Integrin-Targeting Chain-Shaped Nanoparticle

被引：101

作者：

Peiris, Pubudu M. ^{[1
,2
,3
]}

Toy, Randall ^{[1
,3
]}

Doolittle, Elizabeth ^{[1
,3
]}

Pansky, Jenna ^{[1
,3
]}

Abramowski, Aaron ^{[1
,3
]}

Tam, Morgan ^{[1
,3
]}

Vicente, Peter ^{[1
,3
]}

Tran, Emily ^{[1
,3
]}

Hayden, Elliott ^{[1
,3
]}

Camann, Andrew ^{[1
,3
]}

Mayer, Aaron ^{[1
,3
]}

Erokwu, Bernadette O. ^{[2
,3
]}

Berman, Zachary ^{[2
,3
]}

Wilson, David ^{[1
,3
,4
]}

Baskaran, Harihara ^{[4
,5
]}

Flask, Chris A. ^{[1
,2
,3
,4
]}

Keri, Ruth A. ^{[4
,6
]}

Karathanasis, Efstathios ^{[1
,2
,3
,4
]}

机构：

[1] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA

[2] Case Western Reserve Univ, Dept Radiol, Cleveland, OH 44106 USA

[3] Case Western Reserve Univ, Case Ctr Imaging Res, Cleveland, OH 44106 USA

[4] Case Western Reserve Univ, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA

[5] Case Western Reserve Univ, Dept Chem Engn, Cleveland, OH 44106 USA

[6] Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA

来源：

ACS NANO | 2012年 / 6卷 / 10期

关键词：

iron oxide nanoparticle; nanochain; metastasis; integrin targeting; magnetic resonance imaging; SUPERPARAMAGNETIC IRON-OXIDE; TUMOR VASCULAR-PERMEABILITY; BREAST-CANCER; CELL-MIGRATION; MOUSE MODEL; BETA; ANGIOGENESIS; EXPRESSION; PARTICLES; ALPHA(V)BETA(3);

D O I：

10.1021/nn303833p

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

While the enhanced permeability and retention effect may promote the preferential accumulation of nanoparticles into well-vascularized primary tumors, it is ineffective in the case of metastases hidden within a large population of normal cells. Due to their small size, high dispersion to organs, and low vascularization, metastatic tumors are less accessible to targeted nanoparticles. To tackle these challenges, we designed a nanoparticle for vascular targeting based on an alpha(v)beta(3) integrin-targeted nanochain particle composed of four iron oxide nanospheres chemically linked in a linear assembly. The chain-shaped nanoparticles enabled enhanced "sensing" of the tumor-associated remodeling of the vascular bed, offering increased likelihood of specific recognition of metastatic tumors. Compared to spherical nanoparticles, the chain-shaped nanoparticles resulted in superior targeting of alpha(v)beta(3) integrin due to geometrically enhanced multivalent docking. We performed multimodal in vivo imaging (fluorescence molecular tomography and magnetic resonance imaging) in a non-invasive and quantitative manner, which showed that the nanoparticles targeted metastases in the liver and lungs with high specificity in a highly aggressive breast tumor model in mice.

引用

页码：8783 / 8795

页数：13

共 79 条

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