title: Effects of polyethylene glycol spacer length and ligand density on folate receptor targeting of liposomal Doxorubicin in vitro.
abstract: The folate receptor is an attractive target for selective tumor delivery of liposomal doxorubicin (DXR) because it is abundantly expressed in a large percentage of tumors. This study examined the effect of polyethylene glycol (PEG) spacer length and folate ligand density on the targeting ability of folate-modified liposomes. Liposomes were modified with folate-derivatized PEG-distearoylphosphatidylethanolamine with PEG molecular weights of 2000, 3400, or 5000. The association of DXR-loaded liposomes with KB cells, which overexpress the folate receptor, was evaluated by flow cytometry at various ratios of folate modification. A low ratio of folate modification with a sufficiently long PEG chain showed the highest folate receptor-mediated association with the cells, but did not show the highest in vitro cytotoxicity. DXR release from folate-modified liposomes in endosomes might be different. These findings will be useful for designing folate receptor-targeting carriers.
authors.affiliation: Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Kawano
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Maitani