Pulmonary Surfactant Protein A‑Mediated Enrichment of Surface-Decorated Polymeric Nanoparticles in Alveolar Macrophages

• Published in: Molecular pharmaceutics 2016-12, Vol.13 (12), p.4168-4178
• Main Authors: Ruge, Christian A, Hillaireau, Hervé, Grabowski, Nadège, Beck-Broichsitter, Mortiz, Cañadas, Olga, Tsapis, Nicolas, Casals, Cristina, Nicolas, Julien, Fattal, Elias
• Format: Article
• Language: English
• Subjects: Animals; Cells, Cultured; Female; Humans; Macrophages, Alveolar - cytology; Macrophages, Alveolar - metabolism; Mice; Mice, Inbred BALB C; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Polymers - administration & dosage; Polymers - chemistry; Pulmonary Surfactant-Associated Protein A - metabolism; Surface Properties
• ISSN: 1543-8384; 1543-8392
• DOI: 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.