Journal
ACS NANO
Volume 6, Issue 10, Pages 8783-8795Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn303833p
Keywords
iron oxide nanoparticle; nanochain; metastasis; integrin targeting; magnetic resonance imaging
Categories
Funding
- American Cancer Society [IRG-91-022-18]
- Case Comprehensive Cancer Center [P30 CA043703]
- NIH Interdisciplinary Biomedical Imaging Training Program [5T32EB007509]
- NIH Medical Student Research Training grant [T35HL082544]
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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.
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