Nanoparticle Imaging of Integrins on Tumor Cells

Abstract

Nanoparticles 10 to 100 nm in size can deliver large payloads to molecular targets, but undergo slow diffusion and/or slow transport through delivery barriers. To examine the feasibility of nanoparticles targeting a marker expressed in tumor cells, we used the binding of cyclic arginine-glycine-aspartic acid (RGD) nanoparticle targeting integrins on BT-20 tumor as a model system. The goals of this study were: 1) to use nanoparticles to image alpha(V)beta3 integrins expressed in BT-20 tumor cells by fluorescence-based imaging and magnetic resonance imaging, and, 2) to identify factors associated with the ability of nanoparticles to target tumor cell integrins. Three factors were identified: 1) tumor cell integrin expression (the alpha(V)beta3 integrin was expressed in BT-20 cells, but not in 9L cells); 2) nanoparticle pharmacokinetics (the cyclic RGD peptide cross-linked iron oxide had a blood half-life of 180 minutes and was able to escape from the vasculature over its long circulation time); and 3) tumor vascularization (the tumor had a dense capillary bed, with distances of <100 microm between capillaries). These results suggest that nanoparticles could be targeted to the cell surface markers expressed in tumor cells, at least in the case wherein the nanoparticles and the tumor model have characteristics similar to those of the BT-20 tumor employed here.

Gold nanoprisms as a hybrid in vivo cancer theranostic platform for in situ photoacoustic imaging, angiography, and localized hyperthermia

“…RGD peptide can mediate cell adhesion and proliferation and plays an important role in tumor angiogenesis and metastasis, being considerably upregulated in the endothelium during angiogenesis. Therefore, RGD represents a marker for malignancy [18] and has become a useful tool for the targeting of drugs and probes for functionalized imaging contrast agents [19,20].…”

Real-Time Intravital Imaging of RGD−Quantum Dot Binding to Luminal Endothelium in Mouse Tumor Neovasculature

“…This makes them highly conducive to preclinical optical imaging. [1][2][3][4][5][6][7][8] Qdots have been used in living subjects to target tissue-specific vascular biomarkers 3 and cancer cells 1,2,4,5,8 and to identify sentinel lymph nodes in cancer 9-12 with the potential for © Copyright 2008 by the American Chemical Society * Corresponding author: mail, Sanjiv S. Gambhir, MD, PhD, Director, Molecular Imaging Program at Stanford (MIPS), Head, Division of Nuclear Medicine, Professor, Department of Radiology and Bio-X Program, The James H. Clark Center, 318 Campus Dr., East Wing, first Floor, Stanford, CA 94305-5427; phone, 650-725-2309; fax, 650-724-4948; sgambhir@stanford.edu. Supporting Information Available: Videos showing RGD-qdot injection and binding, RGD-qdots in normal mouse vasculature and tumor vasculature, Cy5.5-RGD block of RGD-qdots in tumor, unconjugated qdots entering the tumor vasculature, and Cy5.5 and Cy5.5-RGD leaking out of the tumor neovasculature and descriptions of nanoparticle conjugates, the tumor model, intravital microscopy, statistics, electron microscopy, and U87MG cells incubated with RGD-qdots.…”

“…4,5,[29][30][31] Nonspecific binding in tumors could nevertheless be caused either by nonspecific adsorption of the RGD peptide or by the qdot surface to tumor neovasculature. To control for this, similar peptide RAD was employed on qdots.…”

The role of imaging and molecular imaging in the early detection of metabolic and cardiovascular dysfunctions

“…The first strategy for targeted imaging is to add targeting moieties on the surface of iron oxide nanoparticles directed against known targets on the cell surface, such as a(v)b3 integrin, 106,109 E-selectin 95,96,110,111 or vascular cell addition molecule. 112 In addition to being specific, such contrast media also benefit from biological amplification through cellular trapping.…”