EGFR-Targeted Magnetic Nanoparticle Heaters Kill Cancer Cells without a Perceptible Temperature Rise

被引:276
作者
Creixell, Mar [1 ,2 ]
Bohorquez, Ana C. [1 ]
Torres-Lugo, Madeline [1 ]
Rinaldi, Carlos [1 ]
机构
[1] Univ Puerto Rico, Dept Chem Engn, Mayaguez, PR 00681 USA
[2] Univ Barcelona, Fac Phys, Dept Elect, E-08028 Barcelona, Spain
基金
美国国家科学基金会;
关键词
iron oxide; magnetic nanoparticles; intracellular magnetic fluid hyperthermia; epidermal growth factor; epidermal growth factor receptor; alternating magnetic field; HUMAN BREAST-CANCER; INTRACELLULAR HYPERTHERMIA; THERAPY;
D O I
10.1021/nn201822b
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
It is currently believed that magnetic nanoparticle heaters (MNHs) can kill cancer cells only when the temperature is raised above 43 degrees C due to energy dissipation in an alternating magnetic field. On the other hand, simple heat conduction arguments indicate that in small tumors or single cells the relative rates of energy dissipation and heat conduction result in a negligible temperature rise, thus limiting the potential e MNHs in treating small tumors and metastatic cancer. Here we demonstrate that internalized MNHs conjugated to epidermal growth factor (EGF) and which target the epidermal growth factor receptor (EGFR) do result in a significant (up to 99.9%) reduction in cell viability and clonogenic survival in a thermal heat dose dependent manner, without the need for a perceptible temperature rise. The effect appears to be cell type specific and indicates that magnetic nanoparticles in alternating magnetic fields may effectively kill cancer cells under conditions previously considered as not possible.
引用
收藏
页码:7124 / 7129
页数:6
相关论文
共 25 条
[1]   Biologic effects of heregulin/neu differentiation factor on normal and malignant human breast and ovarian epithelial cells [J].
Aguilar, Z ;
Akita, RW ;
Finn, RS ;
Ramos, BL ;
Pegram, MD ;
Kabbinavar, FF ;
Pietras, RJ ;
Pisacane, P ;
Sliwkowski, MX ;
Slamon, DJ .
ONCOGENE, 1999, 18 (44) :6050-6062
[2]  
ARMSTRONG DK, 1994, CANCER RES, V54, P5280
[3]   Apical epidermal growth factor receptor signaling: Regulation of stretch-dependent exocytosis in bladder umbrella cells [J].
Balestreire, Elena M. ;
Apodaca, Gerard .
MOLECULAR BIOLOGY OF THE CELL, 2007, 18 (04) :1312-1323
[4]   The effect of grafting method on the colloidal stability and in vitro cytotoxicity of carboxymethyl dextran coated magnetic nanoparticles [J].
Creixell, Mar ;
Herrera, Adriana P. ;
Latorre-Esteves, Magda ;
Ayala, Vanessa ;
Torres-Lugo, Madeline ;
Rinaldi, Carlos .
JOURNAL OF MATERIALS CHEMISTRY, 2010, 20 (39) :8539-8547
[5]   Preparation of epidermal growth factor (EGF) conjugated iron oxide nanoparticles and their internalization into colon cancer cells [J].
Creixell, Mar ;
Herrera, Adriana P. ;
Ayala, Vanessa ;
Latorre-Esteves, Magda ;
Perez-Torres, Marianela ;
Torres-Lugo, Madeline ;
Rinaldi, Carlos .
JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS, 2010, 322 (15) :2244-2250
[6]  
DeNardo SJ, 2007, J NUCL MED, V48, P437
[7]   Clonogenic assay of cells in vitro [J].
Franken, Nicolaas A. P. ;
Rodermond, Hans M. ;
Stap, Jan ;
Haveman, Jaap ;
van Bree, Chris .
NATURE PROTOCOLS, 2006, 1 (05) :2315-2319
[8]   INTRACELLULAR HYPERTHERMIA - BIOPHYSICAL APPROACH TO CANCER-TREATMENT VIA INTRACELLULAR TEMPERATURE AND BIOPHYSICAL ALTERATIONS [J].
GORDON, RT ;
HINES, JR ;
GORDON, D .
MEDICAL HYPOTHESES, 1979, 5 (01) :83-102
[9]   Multifunctional superparamagnetic nanocarriers with folate-mediated and pH-responsive targeting properties for anticancer drug delivery [J].
Guo, Miao ;
Que, Chailu ;
Wang, Chenhong ;
Liu, Xiaozhou ;
Yan, Husheng ;
Liu, Keliang .
BIOMATERIALS, 2011, 32 (01) :185-194
[10]   Blood Purification Using Functionalized Core/Shell Nanomagnets [J].
Herrmann, Inge K. ;
Urner, Martin ;
Koehler, Fabian M. ;
Hasler, Melanie ;
Roth-Z'Graggen, Birgit ;
Grass, Robert N. ;
Ziegler, Urs ;
Beck-Schimmer, Beatrice ;
Stark, Wendelin J. .
SMALL, 2010, 6 (13) :1388-1392