Improved drug delivery to cancer cells: a method using magnetoliposomes that target epidermal growth factor receptors.
The toxin delivery system described herein would allow for the selective killing of tumor cells overexpressing the epidermal growth factor receptor (EGFR). Tumor cells often overexpress EGFR, because it allows the cells to divide more quickly. Past delivery systems targeting this receptor have been ineffective due to a lack of specificity that results in harm to surrounding tissue and damage to organs such as the liver. The technique presented here is different, because it presents the possibility of delivering toxin only to the tumor area and almost exclusively to the tumor cells. Delivery is localized to the tumor tissue through the use of EGF conjugated magnetoliposomes. These are liposomes that have magnets imbedded in their bilayer, allowing for selective heating and release of a drug when the magnetoliposome is under an oscillating magnetic field. To create an additional level of specificity, the delivery system will consist of two EGF-bound components that must interact within the endosome of a cell for the toxin to be released. If a tumor cell overexpresses EGFR by 5-fold, then each of its endosomes will have 5 times more receptors than those of a normal cell. Therefore, the tumor cell's endosome has a 5 times greater chance of containing one EGF-bound component and a 25 times greater chance of containing both components. Since both components are necessary for toxin release, the tumor cells will receive 25 times more toxin than the normal cells. Theoretically, it is possible to produce a three or four component system that would deliver 125 or 625 times more toxin to the tumor cells.
Kullberg
M
M
Biomedical Program and Department of Biological Sciences, University of Alaska, 3211 Providence Drive, Anchorage, AK 99508, USA. AFMPK@uaa.alaska.edu
Mann
K
K
Owens
J L
JL
D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000187:drug effects* / Q000378:metabolism; D008081:Liposomes; D008280:Magnetics / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy*; D014118:Toxins, Biological / Q000627:therapeutic use
D008081:Liposomes; D014118:Toxins, Biological; D066246:ErbB Receptors