%0 Journal Article
%A Ruge, Christian 
%A Hillaireau, Hervé
%A Grabowski, Nadège
%A Beck-Broichsitter, Mortiz
%A Cañadas Benito, Olga
%A Tsapis, Nicolas
%A Casals Carro, María Cristina
%A Nicolas, Julien
%A Fattal, Elias
%T Pulmonary surfactant protein A-mediated enrichment of surface-decorated polymeric nanoparticles in alveolar macrophages
%D 2016
%@ 1543-8384
%U https://hdl.handle.net/20.500.14352/94444
%X Surfactant protein A (SP-A), a lung anti-infective protein, is a lectin with affinity for sugars found on fungal and micrococcal surfaces such as mannose. We synthesized a mannosylated poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) copolymer and used it to produce nanoparticles with a polyester (PLGA/PLA) core and a PEG shell decorated with mannose residues, designed to be strongly associated with SP-A for an increased uptake by alveolar macrophages. Nanoparticles made of the copolymers were obtained by nanoprecipitation and displayed a size of around 140 nm. The presence of mannose on the surface was demonstrated by zeta potential changes according to pH and by a strong aggregation in the presence of concanavalin A. Mannosylated nanoparticles bound to SP-A as demonstrated by dynamic light scattering and transmission electron microscopy. The association with SP-A increased nanoparticle uptake by THP-1 macrophages in vitro. In vivo experiments demonstrated that after intratracheal administration of nanoparticles with or without SP-A, SP-A-coated mannosylated nanoparticles were internalized by alveolar macrophages in greater proportion than SP-A-coated nonmannosylated nanoparticles. The data demonstrate for the first time that the pool of nanoparticles available to lung cells can be changed after surface modification, using a biomimetic approach.
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