title: Lysine-tagged peptide coupling onto polylactide nanoparticles coated with activated ester-based amphiphilic copolymer: a route to highly peptide-functionalized biodegradable carriers.
abstract: Efficient biomolecule conjugation to the surface of biodegradable colloidal carriers is crucial for their targeting efficiency in drug/vaccine delivery applications. We here propose a potent strategy to drastically improve peptide immobilization on biodegradable polylactide (PLA) nanoparticles (NPs). Our approach particularly relies on the use of an amphiphilic block copolymer PLA-b-poly(N-acryloxysuccinimide-co-N-vinylpyrrolidone) (PLA-b-P(NAS-co-NVP)) as NP surface modifier, whose the N-succinimidyl (NS) ester functions of the NAS units along the polymer chain ensure N-terminal amine peptide coupling. The well-known immunostimulatory peptide sequence derived from the human interleukin 1β (IL-1β), VQGEESNDK, was coupled on the NPs of 169 nm mean diameter in phosphate buffer (pH 8, 10 mM). A maximum amount of 2 mg immobilized per gram of NPs (i.e. 0.042 peptidenm(-2)) was obtained. Introduction of a three lysine tag at the peptide N-terminus (KKKVQGEESNDK) resulted in a dramatic improvement of the immobilized peptide amounts (27.5 mg/g NP, i.e. 0.417 peptidenm(-2)). As a comparison, the density of tagged peptide achievable on surfactant free PLA NPs of similar size (140 nm), through classical EDC or EDC/NHS activation of the surface PLA carboxylic end-groups, was found to be 6 mg/g NP (i.e. 0.075 peptidenm(-2)), showing the decisive impact of the P(NAS-co-NVP)-based hairy corona for high peptide coupling. These results demonstrate that combined use of lysine tag and PLA-b-P(NAS-co-NVP) surfactant represents a valuable platform to tune and optimize surface bio-functionalization of PLA-based biodegradable carriers.
authors.affiliation: Aix-Marseille Université, CNRS, UMR 7273, Institut de Chimie Radicalaire, Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Handké
authors.forename: Damien
authors.initials: D
authors.lastname: Ficheux
authors.forename: Marion
authors.initials: M
authors.lastname: Rollet
authors.forename: Thierry
authors.initials: T
authors.lastname: Delair
authors.forename: Kamel
authors.initials: K
authors.lastname: Mabrouk
authors.forename: Denis
authors.initials: D
authors.lastname: Bertin
authors.forename: Didier
authors.initials: D
authors.lastname: Gigmes
authors.forename: Bernard
authors.initials: B
authors.lastname: Verrier
authors.forename: Thomas
authors.initials: T
authors.lastname: Trimaille
mesh_terms: D000178:Acrylamides / Q000737:chemistry; D000595:Amino Acid Sequence; D001673:Biodegradation, Environmental; D016923:Cell Death / Q000187:drug effects; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D003102:Colloids; D004337:Drug Carriers / Q000737:chemistry*; D004952:Esters / Q000737:chemistry*; D006801:Humans; D055767:Immobilized Proteins / Q000378:metabolism; D008239:Lysine / Q000378:metabolism*; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011091:Polyesters / Q000737:chemistry*; D011760:Pyrrolidinones / Q000737:chemistry; D055672:Static Electricity; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D000178:Acrylamides; D003102:Colloids; D004337:Drug Carriers; D004952:Esters; D055767:Immobilized Proteins; D010455:Peptides; D011091:Polyesters; D011760:Pyrrolidinones; D013501:Surface-Active Agents; C033616:poly(lactide); C042670:N-vinyl-2-pyrrolidinone; D008239:Lysine