Isabelle Bertholon1, Christine Vauthier, Denis Labarre. 1. Laboratoire de Physico-chimie, Biopharmacie, Pharmacotechnie, UMR CNRS 8612, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296, Châtenay-Malabry, Cedex, France.
Abstract
PURPOSE: Biodistribution of intravenously administered nanoparticles depends on opsonization. The aim of this study was the evaluation of complement activation induced by nanoparticles coated with different polysaccharides. Influences of size and configuration of dextran, dextran sulfate, or chitosan bound onto nanoparticles were investigated. METHOD: Core-shell nanoparticles were prepared by redox radical or anionic polymerization of isobutylcyanoacrylate in the presence of polysaccharides. Conversion of C3 into C3b in serum incubated with nanoparticles was evaluated. RESULTS: Cleavage of C3 increased with size of dextran bound in "loops" configuration, whereas it decreased when dextran was bound in "brush." It was explained by an increasing steric repulsive effect of the brush, inducing poor accessibility to OH groups. The same trend was observed for chitosan-coated nanoparticles. Nanoparticles coated with a brush of chitosan activated the complement system lesser than nanoparticles coated with a brush of dextran. This was explained by an improved repelling effect. Dextran-sulfate-coated nanoparticles induced a low cleavage of C3 whereas it strongly enhanced protein adsorption. CONCLUSION: Complement activation was highly sensitive to surface features of the nanoparticles. Type of polysaccharide, configuration on the surface, and accessibility to reactive functions along chains are critical parameters for complement activation.
PURPOSE: Biodistribution of intravenously administered nanoparticles depends on opsonization. The aim of this study was the evaluation of complement activation induced by nanoparticles coated with different polysaccharides. Influences of size and configuration of dextran, dextran sulfate, or chitosan bound onto nanoparticles were investigated. METHOD: Core-shell nanoparticles were prepared by redox radical or anionic polymerization of isobutylcyanoacrylate in the presence of polysaccharides. Conversion of C3 into C3b in serum incubated with nanoparticles was evaluated. RESULTS: Cleavage of C3 increased with size of dextran bound in "loops" configuration, whereas it decreased when dextran was bound in "brush." It was explained by an increasing steric repulsive effect of the brush, inducing poor accessibility to OH groups. The same trend was observed for chitosan-coated nanoparticles. Nanoparticles coated with a brush of chitosan activated the complement system lesser than nanoparticles coated with a brush of dextran. This was explained by an improved repelling effect. Dextran-sulfate-coated nanoparticles induced a low cleavage of C3 whereas it strongly enhanced protein adsorption. CONCLUSION: Complement activation was highly sensitive to surface features of the nanoparticles. Type of polysaccharide, configuration on the surface, and accessibility to reactive functions along chains are critical parameters for complement activation.
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