Nanoparticle imaging of integrins on tumor cells.
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.
Montet
Xavier
X
Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Montet-Abou
Karin
K
Reynolds
Fred
F
Weissleder
Ralph
R
Josephson
Lee
L
D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000473:pathology*; D002277:Carcinoma / Q000098:blood supply / Q000737:chemistry / Q000473:pathology*; D045744:Cell Line, Tumor / Q000737:chemistry / Q000648:ultrastructure; D003952:Diagnostic Imaging / Q000379:methods; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005240:Feasibility Studies; D005260:Female; D005456:Fluorescent Dyes / Q000032:analysis; D005470:Fluorometry / Q000379:methods*; D018316:Gliosarcoma / Q000737:chemistry / Q000473:pathology*; D006207:Half-Life; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000032:analysis*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D049329:Nanostructures / Q000032:analysis; D009363:Neoplasm Proteins / Q000032:analysis*; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000032:analysis; D010316:Particle Size; D051381:Rats; D014018:Tissue Distribution
D005456:Fluorescent Dyes; D039302:Integrin alphaVbeta3; D009363:Neoplasm Proteins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid