Iron oxide nanoparticles as a drug delivery vehicle for MRI monitored magnetic targeting of brain tumors

被引:692
作者
Chertok, Beata [1 ]
Moffat, Bradford A. [2 ]
David, Allan E. [1 ]
Yu, Faquan [1 ]
Bergemann, Christian [3 ]
Ross, Brian D. [2 ]
Yang, Victor C. [1 ,4 ]
机构
[1] Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Sch Med, Ctr Mol Imaging, Dept Radiol, Ann Arbor, MI 48109 USA
[3] Chemicell GmbH, D-10823 Berlin, Germany
[4] Tianjin Univ, Sch Chem Engn, Tianjin 300072, Peoples R China
关键词
drug delivery; nanoparticle; MRI; magnetism; image analysis;
D O I
10.1016/j.biomaterials.2007.08.050
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
This study explored the possibility of utilizing iron oxide nanoparticles as a drug delivery vehicle for minimally invasive, MRI-monitored magnetic targeting of brain tumors. In vitro determined hydrodynamic diameter of similar to 100nm, saturation magnetization of 94 emu/g Fe and T-2 relaxivity of 43 s(-1) mM(-1) of the nanoparticles suggested their applicability for this purpose. In vivo effect of magnetic targeting on the extent and selectivity of nanoparticle accumulation in tumors of rats harboring orthotopic 9L-gliosarcomas was quantified with MRI. Animals were intravenously injected with nanoparticles (12mg Fe/kg) under a magnetic field density of 0T (control) or 0.4 T (experimental) applied for 30 min. MR images were acquired prior to administration of nanoparticles and immediately after magnetic targeting at I It intervals for 4h. Image analysis revealed that magnetic targeting induced a 5-fold increase in the total glioma exposure to magnetic nanoparticles over non-targeted tumors (p = 0.005) and a 3.6-fold enhancement in the target selectivity index of nanoparticle accumulation in glioma over the normal brain (p = 0.025). In conclusion, accumulation of iron oxide nanoparticles in gliosarcomas can be significantly enhanced by magnetic targeting and successfully quantified by MR imaging. Hence, these nanoparticles appear to be a promising vehicle for glioma-targeted drug delivery. (c) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:487 / 496
页数:10
相关论文
共 46 条
[1]   Magnetic drug targeting - Biodistribution of the magnetic carrier and the chemotherapeutic agent mitoxantrone after locoregional cancer treatment [J].
Alexiou, C ;
Jurgons, R ;
Schmid, RJ ;
Bergemann, C ;
Henke, J ;
Erhardt, W ;
Huenges, E ;
Parak, F .
JOURNAL OF DRUG TARGETING, 2003, 11 (03) :139-149
[2]  
Alexiou C, 2000, CANCER RES, V60, P6641
[3]   Penetration of intra-arterially administered vincristine in experimental brain tumor [J].
Boyle, FM ;
Eller, SL ;
Grossman, SA .
NEURO-ONCOLOGY, 2004, 6 (04) :300-305
[4]  
CHIRAS J, 1988, J NEURORADIOLOGY, V15, P31
[5]   Malignant gliomas in 2005 - Where to GO from here? [J].
Fisher, PG ;
Buffler, PA .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2005, 293 (05) :615-617
[6]   Significant transport of doxorubicin into the brain with polysorbate 80-coated nanoparticles [J].
Gulyaev, AE ;
Gelperina, SE ;
Skidan, IN ;
Antropov, AS ;
Kivman, GY ;
Kreuter, J .
PHARMACEUTICAL RESEARCH, 1999, 16 (10) :1564-1569
[7]   Targeted drug delivery for brain cancer treatment [J].
Gutman, RL ;
Peacock, G ;
Lu, DR .
JOURNAL OF CONTROLLED RELEASE, 2000, 65 (1-2) :31-41
[8]  
Heimberger AB, 2000, CLIN CANCER RES, V6, P4148
[9]   PHYSICAL AND CHEMICAL-PROPERTIES OF SUPERPARAMAGNETIC IRON-OXIDE MR CONTRAST AGENTS - FERUMOXIDES, FERUMOXTRAN, FERUMOXSIL [J].
JUNG, CW ;
JACOBS, P .
MAGNETIC RESONANCE IMAGING, 1995, 13 (05) :661-674
[10]   Intravesical administration of doxorubicin to swine bladder using magnetically targeted carriers [J].
Leakakos, T ;
Ji, C ;
Lawson, G ;
Peterson, C ;
Goodwin, S .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2003, 51 (06) :445-450