Polymeric micelles modified by folate-PEG-lipid for targeted drug delivery to cancer cells in vitro.
A novel technique was developed for the formation of ligand-targeted polymeric micelles that can be applicable to various ligands. For tumor-specific drug delivery, camptothecin (CPT)-loaded polymeric micelles were modified by folate to produce a folate-receptor-targeted drug carrier. Folate-linked PEG5000-distearoylphosphatidylethanolamine (folate-PEG5000-DSPE) was added when preparations of drug-loaded polymeric micelles, resulting in folate ligands exposed to the surface. Folate-modified CPT-loaded polymeric micelles (F-micelle) were evaluated by measuring cellular uptake using a flow cytometer, fluorescence microscopy, and confocal laser scanning microscopy, and by cytotoxicity measurement. The results revealed that F-micelle showed higher cellular uptake in KB cells overexpressing folate receptor (FR) and higher cytotoxicity compared with non-folate modified CPT-loaded polymeric micelles (plain micelles) in KB cells, but not in FR-negative HepG2 cells. This result indicated that polymeric micelles were successfully modified by the folate-linked lipid.
Hayama
Akihiro
A
Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
Yamamoto
Tatsuhiro
T
Yokoyama
Masayuki
M
Kawano
Kumi
K
Hattori
Yoshiyuki
Y
Maitani
Yoshie
Y
D002460:Cell Line; D005434:Flow Cytometry; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D008055:Lipids / Q000737:chemistry*; D008823:Micelles; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000473:pathology*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*
D008055:Lipids; D008823:Micelles; D011108:Polymers; D011092:Polyethylene Glycols; D005492:Folic Acid