Induction of cancer cell-specific apoptosis by folate-labeled cationic liposomes.
We have previously reported that cationic liposomes themselves can induce apoptosis in macrophages and lymphocytes. In this paper, we attempted the cancer cell-specific delivery of cationic liposomes and the induction of apoptosis utilizing this characteristic. Cationic liposomes composed of stearylamine (SA-liposomes) induced apoptosis in human nasopharyngeal epidermoid carcinoma cells (KB cells) overexpressing the folate receptor and human fibroblasts (WI-38 cells) with no folate receptor, without showing selectivity. To recruit liposomes to cancer cells and induce apoptosis, we focused on the folate receptor and prepared folic acid-labeled liposomes using polyethyleneglycol (PEG) (folate-PEG-liposomes). Folate-PEG-liposomes showed selectivity and induced apoptosis in KB cells, but not WI-38 cells. The apoptosis occurred in a dose-dependent manner. Furthermore, folate-PEG-liposomes appear to associate with KB cells via the folate receptor, whereas SA-liposomes may associate with cells through electrostatic interactions. To confirm the contribution of the folate receptor to apoptosis of KB cells induced by folate-PEG-liposomes, the effect of folic acid on the apoptosis was examined. The addition of free folic acid drastically suppressed the apoptosis of KB cells and the percentage of cells with hypodiploid nuclei returned to the control level. Taken together, cationic liposomes labeled with folate bound to KB cells via folate receptors and, interestingly, the cationic liposomes themselves could cause apoptosis in cancer cells.
School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Tomomi
T
Yoshida
Naoko
N
Oide
Takatoshi
T
Sakamoto
Satoshi
S
Yotsumoto
Yoichi
Y
Negishi
Seishi
S
Tsuchiya
Yukihiko
Y
Aramaki
D000588:Amines / Q000737:chemistry / Q000378:metabolism; D017209:Apoptosis; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002412:Cations; D045744:Cell Line, Tumor; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000737:chemistry; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D009303:Nasopharyngeal Neoplasms; D011092:Polyethylene Glycols / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
D000588:Amines; D002352:Carrier Proteins; D002412:Cations; D058973:Folate Receptors, GPI-Anchored; D008081:Liposomes; D011956:Receptors, Cell Surface; D011092:Polyethylene Glycols; D005492:Folic Acid; C009317:stearylamine