title: Imaging metastasis using an integrin-targeting chain-shaped nanoparticle.
abstract: 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 α(v)β(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 α(v)β(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.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Pubudu M
authors.initials: PM
authors.lastname: Peiris
authors.forename: Randall
authors.initials: R
authors.lastname: Toy
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Doolittle
authors.forename: Jenna
authors.initials: J
authors.lastname: Pansky
authors.forename: Aaron
authors.initials: A
authors.lastname: Abramowski
authors.forename: Morgan
authors.initials: M
authors.lastname: Tam
authors.forename: Peter
authors.initials: P
authors.lastname: Vicente
authors.forename: Emily
authors.initials: E
authors.lastname: Tran
authors.forename: Elliott
authors.initials: E
authors.lastname: Hayden
authors.forename: Andrew
authors.initials: A
authors.lastname: Camann
authors.forename: Aaron
authors.initials: A
authors.lastname: Mayer
authors.forename: Bernadette O
authors.initials: BO
authors.lastname: Erokwu
authors.forename: Zachary
authors.initials: Z
authors.lastname: Berman
authors.forename: David
authors.initials: D
authors.lastname: Wilson
authors.forename: Harihara
authors.initials: H
authors.lastname: Baskaran
authors.forename: Chris A
authors.initials: CA
authors.lastname: Flask
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Keri
authors.forename: Efstathios
authors.initials: E
authors.lastname: Karathanasis
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000556:secondary*; D045744:Cell Line, Tumor; D003287:Contrast Media; D005260:Female; D039302:Integrin alphaVbeta3 / Q000737:chemistry*; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000737:chemistry
chemical_list: D003287:Contrast Media; D039302:Integrin alphaVbeta3; D053769:Nanocapsules