Lysine-tagged peptide coupling onto polylactide nanoparticles coated with activated ester-based amphiphilic copolymer: A route to highly peptide-functionalized biodegradable carriers - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Colloids and Surfaces B: Biointerfaces Année : 2013

Lysine-tagged peptide coupling onto polylactide nanoparticles coated with activated ester-based amphiphilic copolymer: A route to highly peptide-functionalized biodegradable carriers

Résumé

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 1 beta (IL-1 beta), 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 peptide nm(-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 peptide nm(-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 peptide nm(-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.

Dates et versions

hal-00872599 , version 1 (14-10-2013)

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Citer

Nadege Handke, Damien Ficheux, Marion Rollet, Thierry Delair, Kamel Mabrouk, et al.. Lysine-tagged peptide coupling onto polylactide nanoparticles coated with activated ester-based amphiphilic copolymer: A route to highly peptide-functionalized biodegradable carriers. Colloids and Surfaces B: Biointerfaces, 2013, 103, pp.298-303. ⟨10.1016/j.colsurfb.2012.10.032⟩. ⟨hal-00872599⟩
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