The binding of plasma proteins to a drug carrier alters the circulation of nanoparticles (NPs) in the bloodstream, and, as a consequence, the anticancer efficiency of the entire nanoparticle drug delivery system. We investigate the possible interaction and the interaction mechanism of a polymeric drug delivery system based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers (pHPMA) with the most abundant proteins in human blood plasma-namely, human serum albumin (HSA), immunoglobulin G (IgG), fibrinogen (Fbg), and apolipoprotein (Apo) E4 and A1-using a combination of small-angle X-ray scattering (SAXS), analytical ultracentrifugation (AUC), and nuclear magnetic resonance (NMR). Through rigorous investigation, we present evidence of weak interactions between proteins and polymeric nanomedicine. Such interactions do not result in the formation of the protein corona and do not affect the efficiency of the drug delivery.

Department of Biochemistry Faculty of Science Charles University Hlavova 2030 8 12840 Prague Czech Republic

Department of Chemistry Lomonosov Moscow State University Leninskie Gory 1 3 119991 Moscow Russia

European Molecular Biology Laboratory Deutsches Elektronen Synchrotron Notkestr 85 22607 Hamburg Germany

Fachgebiet Physik weicher Materie Physik Department Technische Universität München James Franck Str 1 85748 Garching Germany

Harvard John A Paulson School of Engineering and Applied Sciences Harvard University Cambridge MA 02138 USA

Institute of Macromolecular Chemistry Czech Academy of Sciences Heyrovského sq 2 16206 Prague Czech Republic

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