Design and function of a dendrimer-based therapeutic nanodevice targeted to tumor cells through the folate receptor.
OBJECTIVE
We sought to develop nanoscale drug delivery material 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 cell 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.
Quintana
Antonio
A
Center for Biologic Nanotechnology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0648, USA.
Raczka
Ewa
E
Piehler
Lars
L
Lee
Inhan
I
Myc
Andrzej
A
Majoros
Istvan
I
Patri
Anil K
AK
Thomas
Thommey
T
Mulé
James
J
Baker
James R
JR
D002352:Carrier Proteins / Q000378:metabolism*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D058973:Folate Receptors, GPI-Anchored; D006801:Humans; D036103:Nanotechnology / Q000379:methods*; D011956:Receptors, Cell Surface; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002352:Carrier Proteins; D004337:Drug Carriers; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface