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

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• 作者：Christian A. Ruge ; Hervé Hillaireau ; Nadège Grabowski ; Mortiz Beck-Broichsitter ; Olga Cañadas ; Nicolas Tsapis ; Cristina Casals ; Julien Nicolas ; Elias Fattal
• 刊名：Molecular Pharmaceutics
• 出版年：2016
• 出版时间：December 5, 2016
• 年：2016
• 卷：13
• 期：12
• 页码：4168-4178
• 全文大小：624K
• ISSN：1543-8392

文摘

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.