Triblock copolymer coated iron oxide nanoparticle conjugate for tumor integrin targeting.
A key challenge in developing nanoplatform-based molecular imaging is to achieve an optimal pharmacokinetic profile to allow sufficient targeting and to avoid rapid clearance by the reticuloendothelial system (RES). In the present study, iron oxide nanoparticles (IONPs) were coated with a PEGylated amphiphilic triblock copolymer, making them water soluble and function-extendable. These particles were then conjugated with a near-infrared fluorescent (NIRF) dye IRDye800 and cyclic Arginine-Glycine-Aspartic acid (RGD) containing peptide c(RGDyK) for integrin alpha(v)beta(3) targeting. In vitro binding assays confirmed the integrin-specific association between the RGD-particle adducts and U87MG glioblastoma cells. Successful tumor homing in vivo was perceived in a subcutaneous U87MG glioblastoma xenograft model by both magnetic resonance imaging (MRI) and NIRF imaging. Ex vivo histopathological studies also revealed low particle accumulation in the liver, which was attributed to their compact hydrodynamic size and PEGylated coating. In conclusion, we have developed a novel RGD-IONP conjugate with excellent tumor integrin targeting efficiency and specificity as well as limited RES uptake for molecular MRI.
The Molecular Imaging Program at Stanford, Department of Radiology, Biophysics and Bio-X Program, Stanford University, Stanford, CA, USA.
Kai
K
Chen
Jin
J
Xie
Hengyi
H
Xu
Deepak
D
Behera
Mark H
MH
Michalski
Sandip
S
Biswal
Andrew
A
Wang
Xiaoyuan
X
Chen
D000818:Animals; D001672:Biocompatible Materials; D045744:Cell Line, Tumor; D005290:Ferric Compounds / Q000737:chemistry* / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D005909:Glioblastoma / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008422:Materials Testing; D051379:Mice; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism; D013499:Surface Properties; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D001672:Biocompatible Materials; D005290:Ferric Compounds; D005456:Fluorescent Dyes; D016023:Integrins; D009842:Oligopeptides; D011108:Polymers; C000499:ferric oxide; C047981:arginyl-glycyl-aspartic acid