Inhibition of influenza virus activity by multivalent glycoarchitectures with matched sizes |
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Authors: | Papp Ilona Sieben Christian Sisson Adam L Kostka Johanna Böttcher Christoph Ludwig Kai Herrmann Andreas Haag Rainer |
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Affiliation: | 1. Freie Universit?t Berlin, Institut für Chemie und Biochemie, Takustrasse 3, 14195 Berlin (Germany), Fax: (+49)?3083853357;2. Humboldt‐Universit?t zu Berlin, Institut für Biologie/Molekulare Biophysik, Invalidenstrasse 42, 10115 Berlin (Germany);3. Centre for Biomaterial Development and Berlin Brandenburg Centre for Regenerative Therapies (BCRT), Institute of Polymer Research, HZG‐Forschungszentrum Geesthacht GmbH, Kantstrasse 55, 14513 Teltow‐Seehof (Germany);4. Freie Universit?t Berlin, Institut für Chemie und Biochemie, Forschungszentrum für Elektronenmikroskopie, Fabeckstrasse 36a, 14195 Berlin (Germany) |
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Abstract: | We describe the synthesis of a series of sialic acid‐conjugated, polyglycerol‐based nanoparticles with diameters in the range of 1–100 nm. Particle sizes were varied along with the degree of functionalization to match the corresponding virus size and receptor multiplicity in order to achieve maximum efficiency. To build up these architectures, we used biocompatible, hyperbranched polyglycerols as scaffolds and recently developed polyglycerol‐based nanogels, the sizes of which can be varied between 2–4 nm and 40–100 nm, respectively. We demonstrate here that such multivalent nanoparticles inhibit influenza A virus cell binding and fusion and consequently infectivity. The potential of multivalency is evident from larger particles showing very efficient inhibition of viral infection up to 80 %. Indeed, both the size of the nanoparticle and the amount of ligand density are important determinants of inhibition efficiency. The inhibitory activity of the tested polymeric nanoparticles drastically increased with size. Particles with similar dimensions to the virus (50–100 nm) are exceedingly effective. We also observed a saturation point in degree of surface functionalization (i.e. ligand density), above which inhibition was not significantly improved. Our study emphasizes the importance of matching particle sizes and ligand densities to mimic biological surfaces and improve interactions; this is a vital concept underlying multivalent interactions. |
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Keywords: | influenza multivalent inhibition nanogels polyglycerol sialic acids viruses |
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