Tumor-targeted drug delivery and MRI contrast enhancement by chlorotoxin-conjugated iron oxide nanoparticles.
OBJECTIVE
This study examines the capabilities of an actively targeting superparamagnetic nanoparticle to specifically deliver therapeutic and MRI contrast agents to cancer cells.


METHODS
Iron oxide nanoparticles were synthesized and conjugated to both a chemotherapeutic agent, methotrexate, and a targeting ligand, chlorotoxin, through a poly(ethylene glycol) linker. Cytotoxicity of this nanoparticle conjugate was evaluated by Alamar Blue cell viability assays, while tumor-cell specificity was examined in vitro and in vivo by MRI.


CONCLUSIONS
Characterization of these multifunctional nanoparticles confirms the successful attachment of both drug and targeting ligands. The targeting nanoparticle demonstrated preferential accumulation and increased cytotoxicity in tumor cells. Furthermore, prolonged retention of these nanoparticles was observed within tumors in vivo.


CONCLUSIONS
The improved specificity, extended particle retention and increased cytotoxicity toward tumor cells demonstrated by this multifunctional nanoparticle system suggest that it possesses potential for applications in cancer diagnosis and treatment.
Sun
Conroy
C
University of Washington, Department of Materials Science & Engineering, Seattle, WA 98195, USA.
Fang
Chen
C
Stephen
Zachary
Z
Veiseh
Omid
O
Hansen
Stacey
S
Lee
Donghoon
D
Ellenbogen
Richard G
RG
Olson
Jim
J
Zhang
Miqin
M
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005290:Ferric Compounds / Q000737:chemistry*; D006801:Humans; D007089:Image Enhancement; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008727:Methotrexate / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D051379:Mice; D008854:Microscopy, Electron; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D012604:Scorpion Venoms / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D023041:Xenograft Model Antitumor Assays
D000964:Antimetabolites, Antineoplastic; D003287:Contrast Media; D005290:Ferric Compounds; D012604:Scorpion Venoms; C091539:Chlorotoxin; C000499:ferric oxide; D008727:Methotrexate