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

被引:170
作者
Sun, Conroy [1 ]
Fang, Chen [1 ]
Stephen, Zachary [2 ]
Veiseh, Omid [1 ]
Hansen, Stacey [3 ]
Lee, Donghoon [4 ]
Ellenbogen, Richard G. [4 ]
Olson, Jim [3 ]
Zhang, Miqin [1 ,4 ,5 ]
机构
[1] Univ Washington, Dept Mat Sci & Engn, Seattle, WA 98195 USA
[2] Univ Washington, Dept Biochem, Seattle, WA 98195 USA
[3] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA
[4] Univ Washington, Dept Radiol, Seattle, WA 98195 USA
[5] Univ Washington, Dept Neurol, Seattle, WA 98195 USA
关键词
chlorotoxin; drug delivery; iron oxide; magnetic resonance imaging; methotrexate; nanoparticle tumor;
D O I
10.2217/17435889.3.4.495
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:495 / 505
页数:11
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