Functionalization of iron oxide magnetic nanoparticles with targeting ligands: their physicochemical properties and in vivo behavior.
OBJECTIVE
To develop and evaluate two tumor-specific nanoprobes by functionalization of a polyethylene glycol-immobilized nanoparticle with arginine-glycine-aspartic acid (RGD) or chlorotoxin ligand that targets α(v)β(3) integrin and matrix metalloproteinase-2 receptors, respectively.


METHODS
The nanoprobes were made of iron oxide cores, biocompatible polymer coating, and surface-conjugated RGD or chlorotoxin peptide. The tumor-targeting specificity of the nanoprobes was evaluated both in vitro and in vivo.


CONCLUSIONS
Both nanoprobes were highly dispersive and exhibited excellent long-term stability in cell culture media. The RGD-conjugated nanoprobe displayed a strong initial accumulation near neovasculatures in tumors followed by quick clearance. Conversely, the chlorotoxin-enabled nanoprobe exhibited sustained accumulation throughout the tumor.


CONCLUSIONS
These findings revealed the influence of the targeting ligands on the intratumoral distribution of the ligand-enabled nanoprobes. With flexible surface chemistry, our nanoparticle platform can be used in a modular fashion to conjugate biomolecules for intended applications.
Department of Materials Science & Engineering, University of Washington, Seattle, WA 98195, USA.
Chen
C
Fang
Omid
O
Veiseh
Forrest
F
Kievit
Narayan
N
Bhattarai
Freddy
F
Wang
Zach
Z
Stephen
Chun
C
Li
Donghoon
D
Lee
Richard G
RG
Ellenbogen
Miqin
M
Zhang
D000818:Animals; D045744:Cell Line, Tumor; D005290:Ferric Compounds / Q000737:chemistry* / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008280:Magnetics; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009842:Oligopeptides / Q000737:chemistry
D005290:Ferric Compounds; D009842:Oligopeptides; C000499:ferric oxide; C047981:arginyl-glycyl-aspartic acid