Design and function of a dendrimer-based therapeutic nanodevice targeted to tumor cells through the folate receptor

被引:511
作者
Quintana, A [1 ]
Raczka, E [1 ]
Piehler, L [1 ]
Lee, I [1 ]
Myc, A [1 ]
Majoros, I [1 ]
Patri, AK [1 ]
Thomas, T [1 ]
Mulé, J [1 ]
Baker, JR [1 ]
机构
[1] Univ Michigan, Sch Med, Dept Internal Med, Ctr Biol Nanotechnol, Ann Arbor, MI 48109 USA
关键词
dendrimer; nanotechnology; chemotherapeutic molecular modeling; methotrexate;
D O I
10.1023/A:1020398624602
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Purpose. We sought to develop nanoscale drug delivery materials that would allow targeted intracellular delivery while having an imaging capability for tracking uptake of the material. A complex nanodevice was designed and synthesized that targets tumor cells through the folate receptor. Methods. The device is based on an ethylenediamine core polyamidoamine dendrimer of generation 5. Folic acid, fluorescein, and methotrexate were covalently attached to the surface to provide targeting, imaging, and intracellular drug delivery capabilities. Molecular modeling determined the optimal dendrimer surface modification for the function of the device and suggested a surface modification that improved targeting. Results. Three nanodevices were synthesized. Experimental targeting data in KB cells confirmed the modeling predictions of specific and highly selective binding. Targeted delivery improved the cytotoxic response of the cells to methotrexate 100-fold over free drug. Conclusions. These results demonstrate the ability to design and produce polymer-based nanodevices for the intracellular targeting of drugs, imaging agents, and other materials.
引用
收藏
页码:1310 / 1316
页数:7
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