title: Peptide Anchor for Folate-Targeted Liposomal Delivery.
abstract: Specific folate receptors are abundantly overexpressed in chronically activated macrophages and in most cancer cells. Directed folate receptor targeting using liposomes is usually achieved using folate linked to a phospholipid or cholesterol anchor. This link is formed using a large spacer like polyethylene glycol. Here, we report an innovative strategy for targeted liposome delivery that uses a hydrophobic fragment of surfactant protein D linked to folate. Our proposed spacer is a small 4 amino acid residue linker. The peptide conjugate inserts deeply into the lipid bilayer without affecting liposomal integrity, with high stability and specificity. To compare the drug delivery potential of both liposomal targeting systems, we encapsulated the nuclear dye Hoechst 34580. The eventual increase in blue fluorescence would only be detectable upon liposome disruption, leading to specific binding of this dye to DNA. Our delivery system was proven to be more efficient (2-fold) in Caco-2 cells than classic systems where the folate moiety is linked to liposomes by polyethylene glycol.
authors.affiliation: CBMA - Centre of Molecular and Environmental Biology, Department of Biology, University of Minho , Braga 4710-057, Portugal.|CEB - Centre of Biological Engineering, University of Minho , Braga 4710-057, Portugal.
authors.forename: Eugénia
authors.initials: E
authors.lastname: Nogueira
authors.affiliation: IQUIFIB - Instituto de Química y Fisicoquímica Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, CONICET , 1113 Buenos Aires, Argentina.
authors.forename: Irene C
authors.initials: IC
authors.lastname: Mangialavori
authors.affiliation: CBMA - Centre of Molecular and Environmental Biology, Department of Biology, University of Minho , Braga 4710-057, Portugal.|CEB - Centre of Biological Engineering, University of Minho , Braga 4710-057, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Loureiro
authors.affiliation: CEB - Centre of Biological Engineering, University of Minho , Braga 4710-057, Portugal.
authors.forename: Nuno G
authors.initials: NG
authors.lastname: Azoia
authors.affiliation: CEB - Centre of Biological Engineering, University of Minho , Braga 4710-057, Portugal.
authors.forename: Marisa P
authors.initials: MP
authors.lastname: Sárria
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto , Porto, Portugal.|IBMC - Instituto de Biologia Molecular e Celular , 4150-180 Porto, Portugal.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Nogueira
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto , Porto, Portugal.|IBMC - Instituto de Biologia Molecular e Celular , 4150-180 Porto, Portugal.
authors.forename: Jaime
authors.initials: J
authors.lastname: Freitas
authors.affiliation: Department of Biosciences and Nutrition, The Royal Institute of Technology, School of Technology and Health, Karolinska Institutet , S-14183 Huddinge, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Härmark
authors.affiliation: Department of Chemistry, University of Cambridge , Cambridge CB2 1EW, United Kingdom.
authors.forename: Ulyana
authors.initials: U
authors.lastname: Shimanovich
authors.affiliation: Institute of Environmental Biotechnology, University of Natural Resources and Life Sciences , 3430 Tulln, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rollett
authors.affiliation: INERIS - Institut National de l'Environnement Industriel et des Risques , 60550 Verneuil en Halatte, France.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Lacroix
authors.affiliation: Department of Chemistry, University of Cambridge , Cambridge CB2 1EW, United Kingdom.
authors.forename: Gonçalo J L
authors.initials: GJ
authors.lastname: Bernardes
authors.affiliation: Institute of Environmental Biotechnology, University of Natural Resources and Life Sciences , 3430 Tulln, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Guebitz
authors.affiliation: Department of Biosciences and Nutrition, The Royal Institute of Technology, School of Technology and Health, Karolinska Institutet , S-14183 Huddinge, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Hebert
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto , Porto, Portugal.|IBMC - Instituto de Biologia Molecular e Celular , 4150-180 Porto, Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Moreira
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto , Porto, Portugal.|IBMC - Instituto de Biologia Molecular e Celular , 4150-180 Porto, Portugal.|ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto , 4099-003 Porto, Portugal.
authors.forename: Alexandre M
authors.initials: AM
authors.lastname: Carmo
authors.affiliation: IQUIFIB - Instituto de Química y Fisicoquímica Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, CONICET , 1113 Buenos Aires, Argentina.
authors.forename: Juan Pablo F C
authors.initials: JP
authors.lastname: Rossi
authors.affiliation: CBMA - Centre of Molecular and Environmental Biology, Department of Biology, University of Minho , Braga 4710-057, Portugal.
authors.forename: Andreia C
authors.initials: AC
authors.lastname: Gomes
authors.affiliation: CBMA - Centre of Molecular and Environmental Biology, Department of Biology, University of Minho , Braga 4710-057, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Preto
authors.affiliation: CEB - Centre of Biological Engineering, University of Minho , Braga 4710-057, Portugal.
authors.forename: Artur
authors.initials: A
authors.lastname: Cavaco-Paulo
mesh_terms: D018938:Caco-2 Cells; D002784:Cholesterol / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005492:Folic Acid / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry / Q000494:pharmacology; D008081:Liposomes; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D010743:Phospholipids / Q000737:chemistry / Q000494:pharmacology
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D010455:Peptides; D010743:Phospholipids; D005492:Folic Acid; D002784:Cholesterol