Imaging Metastasis Using an Integrin-Targeting Chain-Shaped Nanoparticle

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• 作者：Pubudu M. Peiris ; Randall Toy ; Elizabeth Doolittle ; Jenna Pansky ; Aaron Abramowski ; Morgan Tam ; Peter Vicente ; Emily Tran ; Elliott Hayden ; Andrew Camann ; Aaron Mayer ; Bernadette O. Erokwu ; Zachary Berman ; David Wilson ; Harihara Baskaran ; Chris A. Flask ; Ruth A. Keri ; Efstathios Karathanasis
• 刊名：ACS Nano
• 出版年：2012
• 出版时间：October 23, 2012
• 年：2012
• 卷：6
• 期：10
• 页码：8783-8795
• 全文大小：719K
• 年卷期：v.6,no.10(October 23, 2012)
• ISSN：1936-086X

文摘

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 伪b>vb>尾b>3b> integrin-targeted nanochain particle composed of four iron oxide nanospheres chemically linked in a linear assembly. The chain-shaped nanoparticles enabled enhanced 鈥渟ensing鈥?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 伪b>vb>尾b>3b> 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.<br>

Keywords:

bs.acs.org/action/doSearch?action=search&searchText=iron+oxide+nanoparticle&qsSearchArea=searchText">iron oxide nanoparticle; bs.acs.org/action/doSearch?action=search&searchText=nanochain&qsSearchArea=searchText">nanochain; bs.acs.org/action/doSearch?action=search&searchText=metastasis&qsSearchArea=searchText">metastasis; bs.acs.org/action/doSearch?action=search&searchText=integrin+targeting&qsSearchArea=searchText">integrin targeting; bs.acs.org/action/doSearch?action=search&searchText=magnetic+resonance+imaging&qsSearchArea=searchText">magnetic resonance imaging