Immunoglobulin deposition on biomolecule corona determines complement opsonization efficiency of preclinical and clinical nanoparticles.

Autor: Vu VP; Translational Bio-Nanosciences Laboratory, The Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Gifford GB; Translational Bio-Nanosciences Laboratory, The Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Chen F; Department of Gastrointestinal Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, China., Benasutti H; Translational Bio-Nanosciences Laboratory, The Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Wang G; Translational Bio-Nanosciences Laboratory, The Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Colorado Center for Nanomedicine and Nanosafety, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Groman EV; Translational Bio-Nanosciences Laboratory, The Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Colorado Center for Nanomedicine and Nanosafety, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Scheinman R; Colorado Center for Nanomedicine and Nanosafety, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Saba L; Systems Genetics and Bioinformatics Laboratory, The Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Center for Translational Pharmacokinetics and Pharmacogenomics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Moghimi SM; Colorado Center for Nanomedicine and Nanosafety, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; School of Pharmacy, The Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.; Division of Stratified Medicine, Biomarkers and Therapeutics, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK., Simberg D; Translational Bio-Nanosciences Laboratory, The Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. dmitri.simberg@ucdenver.edu.; Colorado Center for Nanomedicine and Nanosafety, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. dmitri.simberg@ucdenver.edu.
Jazyk: angličtina
Zdroj: Nature nanotechnology [Nat Nanotechnol] 2019 Mar; Vol. 14 (3), pp. 260-268. Date of Electronic Publication: 2019 Jan 14.
DOI: 10.1038/s41565-018-0344-3
Abstrakt: Deposition of complement factors (opsonization) on nanoparticles may promote clearance from the blood by macrophages and trigger proinflammatory responses, but the mechanisms regulating the efficiency of complement activation are poorly understood. We previously demonstrated that opsonization of superparamagnetic iron oxide (SPIO) nanoworms with the third complement protein (C3) was dependent on the biomolecule corona of the nanoparticles. Here we show that natural antibodies play a critical role in C3 opsonization of SPIO nanoworms and a range of clinically approved nanopharmaceuticals. The dependency of C3 opsonization on immunoglobulin binding is almost universal and is observed regardless of the complement activation pathway. Only a few surface-bound immunoglobulin molecules are needed to trigger complement activation and opsonization. Although the total amount of plasma proteins adsorbed on nanoparticles does not determine C3 deposition efficiency, the biomolecule corona per se enhances immunoglobulin binding to all nanoparticle types. We therefore show that natural antibodies represent a link between biomolecule corona and C3 opsonization, and may determine individual complement responses to nanomedicines.
Databáze: MEDLINE
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