title: Targeted delivery via avidin fusion protein: intracellular fate of biotinylated doxorubicin derivative and cellular uptake kinetics and biodistribution of biotinylated liposomes.
abstract: In this study, avidin-biotin technology was combined with a multifunctional drug carrier modality i.e. liposomes to achieve an active and versatile targeting approach. The anti-cancer drug doxorubicin (DOX) was modified with direct biotinylation (B-DOX) (Allart et al., 2003), or encapsulated in biotinylated sterically stabilized pH-sensitive liposomes (BL-DOX), and targeted to the lentiviral vector transduced cells expressing an avidin fusion protein on the cell membrane (Lehtolainen et al., 2003; Lesch et al., 2009). The direct biotinylation of doxorubicin improved cell internalization in rat glioma (BT4C) cells expressing avidin fusion protein receptor but cell toxicity was reduced by 78-fold due to impaired nuclear localization. In contrast, liposomal formulations restored the biological activity of the DOX in several cell lines. However, mainly due to uptake via non-specific pathways the active targeting of BL-DOX was negligible in both in vitro and in vivo studies. Active targeting with multifunctional drug carrier systems is challenging and further studies will be needed to optimize the properties of targeted drug carrier and receptor expression systems.
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio Campus, Finland.
authors.forename: Suvi K
authors.initials: SK
authors.lastname: Soininen
authors.forename: Pauliina
authors.initials: P
authors.lastname: Lehtolainen-Dalkilic
authors.forename: Tanja
authors.initials: T
authors.lastname: Karppinen
authors.forename: Tiina
authors.initials: T
authors.lastname: Puustinen
authors.forename: Galina
authors.initials: G
authors.lastname: Dragneva
authors.forename: Minna U
authors.initials: MU
authors.lastname: Kaikkonen
authors.forename: Marjo
authors.initials: M
authors.lastname: Jauhiainen
authors.forename: Brigitte
authors.initials: B
authors.lastname: Allart
authors.forename: David L
authors.initials: DL
authors.lastname: Selwood
authors.forename: Thomas
authors.initials: T
authors.lastname: Wirth
authors.forename: Hanna P
authors.initials: HP
authors.lastname: Lesch
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Määttä
authors.forename: Jukka
authors.initials: J
authors.lastname: Mönkkönen
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
authors.forename: Marika
authors.initials: M
authors.lastname: Ruponen
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001360:Avidin / Q000008:administration & dosage* / Q000235:genetics; D001710:Biotin / Q000008:administration & dosage* / Q000235:genetics; D019921:Biotinylation; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007700:Kinetics; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D014018:Tissue Distribution
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D011993:Recombinant Fusion Proteins; D001360:Avidin; D001710:Biotin; D004317:Doxorubicin