title: Selective delivery of folate-PEG-linked, nanoemulsion-loaded aclacinomycin A to KB nasopharyngeal cells and xenograft: effect of chain length and amount of folate-PEG linker.
abstract: To investigate the use of folate-targeted nanoemulsion-loaded aclacinomycin A (ACM) to folate receptor (FR)-positive cells, we attempted to optimize the targeting ability of nanoemulsions by modifying the chain length and amount of the folate-PEG linker. Folate-linked, nanoemulsion-loaded ACM were formulated with 0.24 mol% of folate-poly (ethylene glycol)(3400)- (folate-PEG(3400)-) and folate-PEG(5000)-distearoylphosphatidylethanolamine (DSPE), and 0.03 mol% of folate-PEG(5000)-DSPE in nanoemulsions. Selective FR-mediated uptake was achieved in a human nasopharyngeal tumor cell line, KB, which overexpresses FR, but not in a human hepatoblastoma cell line, (FR(-)) HepG2. At the same amount of folate modification, the association with KB cells was increased with increasing the PEG-chain length. The association of 0.03 and 0.24 mol% folate-PEG(5000)-linked nanoemulsions with cells was 5- and 3.3-fold higher than that of non-folate nanoemulsion, respectively, while their cytotoxicity was similar. Both 0.03 and 0.24 mol% folate-PEG(5000)-linked nanoemulsions and non-folate nanoemulsion following intravenous injection inhibited tumor growth more significantly than ACM solution on day 24 following tumor inoculation (p < 0.01). This study demonstrates that a folate-linked nanoemulsion is feasible for tumor-targeted ACM delivery, and that folate modification with a sufficiently long PEG-chain and a small amount of nanoemulsion is an effective way of targeting nanoemulsion to tumor cells.
authors.affiliation: Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan.
authors.forename: Yukino
authors.initials: Y
authors.lastname: Ohguchi
authors.forename: Kumi
authors.initials: K
authors.lastname: Kawano
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hattori
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Maitani
mesh_terms: D015250:Aclarubicin / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005260:Female; D005492:Folic Acid / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D049329:Nanostructures; D009305:Nasopharynx / Q000166:cytology; D009369:Neoplasms / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms; D014183:Transplantation, Heterologous
chemical_list: D000903:Antibiotics, Antineoplastic; D011092:Polyethylene Glycols; D015250:Aclarubicin; D005492:Folic Acid