title: Pulmonary Surfactant Protein A-Mediated Enrichment of Surface-Decorated Polymeric Nanoparticles in Alveolar Macrophages.
abstract: 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.
authors.affiliation: Institut Galien Paris-Sud, Univ. Paris-Sud, CNRS, Université Paris-Saclay , 92296 Châtenay-Malabry, France.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Ruge
authors.affiliation: Institut Galien Paris-Sud, Univ. Paris-Sud, CNRS, Université Paris-Saclay , 92296 Châtenay-Malabry, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Hillaireau
authors.affiliation: Institut Galien Paris-Sud, Univ. Paris-Sud, CNRS, Université Paris-Saclay , 92296 Châtenay-Malabry, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Grabowski
authors.affiliation: Institut Galien Paris-Sud, Univ. Paris-Sud, CNRS, Université Paris-Saclay , 92296 Châtenay-Malabry, France.
authors.forename: Mortiz
authors.initials: M
authors.lastname: Beck-Broichsitter
authors.affiliation: Department of Biochemistry and Molecular Biology I, Universidad Complutense , 28040 Madrid, Spain.|CIBER de Enfermedades Respiratorias, Universidad Complutense , 28040 Madrid, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Cañadas
authors.affiliation: Institut Galien Paris-Sud, Univ. Paris-Sud, CNRS, Université Paris-Saclay , 92296 Châtenay-Malabry, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tsapis
authors.affiliation: Department of Biochemistry and Molecular Biology I, Universidad Complutense , 28040 Madrid, Spain.|CIBER de Enfermedades Respiratorias, Universidad Complutense , 28040 Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Casals
authors.affiliation: Institut Galien Paris-Sud, Univ. Paris-Sud, CNRS, Université Paris-Saclay , 92296 Châtenay-Malabry, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Nicolas
authors.affiliation: Institut Galien Paris-Sud, Univ. Paris-Sud, CNRS, Université Paris-Saclay , 92296 Châtenay-Malabry, France.
authors.forename: Elias
authors.initials: E
authors.lastname: Fattal
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016676:Macrophages, Alveolar / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism*; D013499:Surface Properties
chemical_list: D011108:Polymers; D037662:Pulmonary Surfactant-Associated Protein A
keywords: lungs; macrophages; mannose; nanoparticles; surfactant protein A