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

Author:

Sun Conroy1,Fang Chen1,Stephen Zachary2,Veiseh Omid1,Hansen Stacey3,Lee Donghoon4,Ellenbogen Richard G4,Olson Jim3,Zhang Miqin145

Affiliation:

1. University of Washington, Department of Materials Science & Engineering, Seattle, WA 98195, USA

2. University of Washington, Department of Biochemistry, Seattle, WA98195, USA

3. Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA 98109, USA

4. University of Washington, Department of Radiology, Seattle, WA 98195, USA

5. University of Washington, Department of Neurological Surgery, Seattle, WA 98195, USA.

Abstract

Aims: This study examines the capabilities of an actively targeting superparamagnetic nanoparticle to specifically deliver therapeutic and MRI contrast agents to cancer cells. Materials & 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. Results & discussion: 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. Conclusion: 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.

Publisher

Future Medicine Ltd

Subject

Development,General Materials Science,Biomedical Engineering,Medicine (miscellaneous),Bioengineering

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