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oai:docta.ucm.es:20.500.14352/944442025-08-29T14:11:40Zcom_20.500.14352_14col_20.500.14352_15

Ruge, Christian Hillaireau, Hervé Grabowski, Nadège Beck-Broichsitter, Mortiz Cañadas Benito, Olga Tsapis, Nicolas Casals Carro, María Cristina Nicolas, Julien Fattal, Elias 2024-01-22T15:10:02Z 2024-01-22T15:10:02Z 2016 Ruge C, Hillaireau H, Grabowski N, Beck-Broichsitter M, Cañadas O, Tsapis N, Casals C, Nicolas J, Fattal E. Pulmonary surfactant protein A – mediated enrichment of surface-decorated polymeric nanoparticles in alveolar macrophages. Mol. Pharmaceutics. 2016 Dec 5;13(12): 4168-4178 1543-8384 10.1021/acs.molpharmaceut.6b00773 https://hdl.handle.net/20.500.14352/94444 1543-8392 https://doi.org/10.1021/acs.molpharmaceut.6b00773 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. eng restricted access Pulmonary surfactant protein A-mediated enrichment of surface-decorated polymeric nanoparticles in alveolar macrophages journal article