title: Size controlled protein nanoemulsions for active targeting of folate receptor positive cells.
abstract: Bovine serum albumin (BSA) nanoemulsions were produced by high pressure homogenization with a tri-block copolymer (Poloxamer 407), which presents a central hydrophobic chain of polyoxypropylene (PPO) and two identical lateral hydrophilic chains of polyethylene glycol (PEG). We observed a linear correlation between tri-block copolymer concentration and size - the use of 5mg/mL of Poloxamer 407 yields nanoemulsions smaller than 100nm. Molecular dynamics and fluorescent tagging of the tri-block copolymer highlight their mechanistic role on the size of emulsions. This novel method enables the fabrication of highly stable albumin emulsions in the nano-size range, highly desirable for controlled drug delivery. Folic Acid (FA)-tagged protein nanoemulsions were shown to promote specific folate receptor (FR)-mediated targeting in FR positive cells. The novel strategy presented here enables the construction of size controlled, functionalized protein-based nanoemulsions with excellent characteristics for active targeting in cancer therapy.
authors.affiliation: CEB - Centre of Biological Engineering, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal; CBMA (Centre of Molecular and Environmental Biology), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Loureiro
authors.affiliation: CEB - Centre of Biological Engineering, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal; CBMA (Centre of Molecular and Environmental Biology), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal.
authors.forename: Eugénia
authors.initials: E
authors.lastname: Nogueira
authors.affiliation: CEB - Centre of Biological Engineering, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal.
authors.forename: Nuno G
authors.initials: NG
authors.lastname: Azoia
authors.affiliation: CEB - Centre of Biological Engineering, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal; CBMA (Centre of Molecular and Environmental Biology), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal.
authors.forename: Marisa P
authors.initials: MP
authors.lastname: Sárria
authors.affiliation: CEB - Centre of Biological Engineering, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal.
authors.forename: Ana S
authors.initials: AS
authors.lastname: Abreu
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Ulyana
authors.initials: U
authors.lastname: Shimanovich
authors.affiliation: University of Natural Resources and Life Sciences, Institute for Environmental Biotechnology, IFA Tulln, Konrad Lorenz Straße 20, 3430 Tulln, Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rollett
authors.affiliation: Department of Biosciences and Nutrition, The Royal Institute of Technology, School of Technology and Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Härmark
authors.affiliation: Department of Biosciences and Nutrition, The Royal Institute of Technology, School of Technology and Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Hebert
authors.affiliation: University of Natural Resources and Life Sciences, Institute for Environmental Biotechnology, IFA Tulln, Konrad Lorenz Straße 20, 3430 Tulln, Vienna, Austria; Austrian Centre of Industrial Biotechnology, Petersgasse 14, 8010 Graz, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Guebitz
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom; Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal.
authors.forename: Gonçalo J L
authors.initials: GJL
authors.lastname: Bernardes
authors.affiliation: CBMA (Centre of Molecular and Environmental Biology), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Preto
authors.affiliation: CBMA (Centre of Molecular and Environmental Biology), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal.
authors.forename: Andreia C
authors.initials: AC
authors.lastname: Gomes
authors.affiliation: CEB - Centre of Biological Engineering, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal. Electronic address: artur@deb.uminho.pt.
authors.forename: Artur
authors.initials: A
authors.lastname: Cavaco-Paulo
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D002460:Cell Line; D016503:Drug Delivery Systems; D004655:Emulsions; D058973:Folate Receptors, GPI-Anchored / Q000187:drug effects*; D005492:Folic Acid / Q000378:metabolism; D006801:Humans; D053758:Nanoparticles; D010316:Particle Size; D020442:Poloxamer; D011092:Polyethylene Glycols; D011108:Polymers; D011409:Propylene Glycols; D011506:Proteins / Q000737:chemistry* / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004655:Emulsions; D058973:Folate Receptors, GPI-Anchored; D011108:Polymers; D011409:Propylene Glycols; D011506:Proteins; D020442:Poloxamer; C012504:polypropylene glycol; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D005492:Folic Acid
keywords: Active targeting; Folic acid; High pressure homogenization; PEGylated surfactant; Protein-based nanoemulsions