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 αvβ3 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 αvβ3 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.

The effects of particle size, shape, density and flow characteristics on particle margination to vascular walls in cardiovascular diseases

“…been developed and constructed from three to four nanospheres covalently linked together for microvascular targeting in the diagnosis and treatment of cancerous and metastasis diseases [77][78][79][80][81][82][83]. However, there have been no reports on the use of nanochains in atherosclerosis.…”

“…This can be explained by the longer circulation of oblongs in the blood compared to spheres. In addition, elongated particles are subjected to torque forces within blood flow, and therefore, they have a tendency to tumble out of the general circulation and scavenge along vessel walls [40,73,77,87] (Figure 5(a)). Spherical particles, on the other hand, tend to follow the streamlines.…”

Targeted superparamagnetic iron oxide nanoparticles for early detection of cancer: Possibilities and challenges

“…In order to detect the metastatic cells, Peiris et al, 136 designed chain shaped iron oxide NPs consisting of four iron oxide nanosphere connected to each other in aligned direction. The chain shaped iron oxide NPs were functionalized by cyclic tripeptide arginine, glycine, glycine, aspartic acid that specifically attach to α v β 3 integrin.…”

New Frontiers in Retinal Imaging

“…The C-C chemokine receptor 3 (CCR3) is a promising biomarker of choroidal neovascularization (CNV), as demonstrated by CCR3 expression on choroidal neovascular endothelial cells in human CNV specimens [123] . Other promising biomarkers include targeting proliferating endothelial, endoglin [124] , and integrin αvβ3 [125,126] . These have been successfully imaged in patient specimens ex vivo and in cardiovascular diseases and cancer.…”