Tumor-targeted drug delivery and MRI contrast enhancement by chlorotoxin-conjugated iron oxide nanoparticles

• Published in: Nanomedicine (London, England) Vol. 3; no. 4; pp. 495 - 505
• Main Authors: Sun, Conroy, Fang, Chen, Stephen, Zachary, Veiseh, Omid, Hansen, Stacey, Lee, Donghoon, Ellenbogen, Richard G, Olson, Jim, Zhang, Miqin
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.08.2008
• Subjects: Animals; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - chemistry; Antimetabolites, Antineoplastic - therapeutic use; Cancer; Cell Line; Cell Line, Tumor; Cell Survival - drug effects; Chemotherapy; chlorotoxin; Contrast media; Contrast Media - administration & dosage; Contrast Media - chemistry; Cytotoxicity; Drug delivery; Drug Delivery Systems - methods; Ferric Compounds - chemistry; Humans; Image Enhancement; iron oxide; iron oxides; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Methotrexate; Methotrexate - administration & dosage; Methotrexate - chemistry; Methotrexate - therapeutic use; Mice; Microscopy, Electron; nanoparticle; nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Nanoparticles - ultrastructure; nanotechnology; Neoplasms - drug therapy; Neoplasms - pathology; Scorpion Venoms - chemistry; Spectroscopy, Fourier Transform Infrared; tumor; Tumor cells; Tumors; Xenograft Model Antitumor Assays
• ISSN: 1743-5889; 1748-6963
• DOI: 10.2217/17435889.3.4.495

This study examines the capabilities of an actively targeting superparamagnetic nanoparticle to specifically deliver therapeutic and MRI contrast agents to cancer cells. 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 and by MRI. 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 . 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.