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

[Display omitted] ► IL-1β derived peptide was coupled on PLA particles coated with activated ester-based polymer. ► Introduction of a 3-lysine tag resulted in a strong increase of the peptide density. ► Tagged peptide density was much higher on polymer coated particles than on naked ones. ► Lysine tag/polymer coating is a versatile platform to improve peptide immobilization. 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 169nm mean diameter in phosphate buffer (pH 8, 10mM). A maximum amount of 2mg immobilized per gram of NPs (i.e. 0.042peptidenm−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 (27.5mg/g NP, i.e. 0.417peptidenm−2). As a comparison, the density of tagged peptide achievable on surfactant free PLA NPs of similar size (140nm), through classical EDC or EDC/NHS activation of the surface PLA carboxylic end-groups, was found to be 6mg/g NP (i.e. 0.075peptidenm−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.