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Molecular Mechanisms of the Interactions of N-(2-Hydroxypropyl)methacrylamide Copolymers Designed for Cancer Therapy with Blood Plasma Proteins

L. Janisova, A. Gruzinov, OV. Zaborova, N. Velychkivska, O. Vaněk, P. Chytil, T. Etrych, O. Janoušková, X. Zhang, C. Blanchet, CM. Papadakis, DI. Svergun, SK. Filippov,

. 2020 ; 12 (2) : . [pub] 20200128

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc20005267

Grantová podpora
17-009735 Grantová Agentura České Republiky
15-10527J Grantová Agentura České Republiky
Pa771/17-1 Deutsche Forschungsgemeinschaft
UNCE 204025/2012 Grantová Agentura, Univerzita Karlova
LTC17065 Ministry of Education, Youth and Sports of the Czech Republic
POLYMAT LO1507 Ministry of Education, Youth and Sports of CR
17-13283S Grantová Agentura České Republiky

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.

Citace poskytuje Crossref.org

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$a The binding of plasma proteins to a drug carrier alters the circulation of nanoparticles (NPs) in the bloodstream, and, as a consequence, the anticancer efficiency of the entire nanoparticle drug delivery system. We investigate the possible interaction and the interaction mechanism of a polymeric drug delivery system based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers (pHPMA) with the most abundant proteins in human blood plasma-namely, human serum albumin (HSA), immunoglobulin G (IgG), fibrinogen (Fbg), and apolipoprotein (Apo) E4 and A1-using a combination of small-angle X-ray scattering (SAXS), analytical ultracentrifugation (AUC), and nuclear magnetic resonance (NMR). Through rigorous investigation, we present evidence of weak interactions between proteins and polymeric nanomedicine. Such interactions do not result in the formation of the protein corona and do not affect the efficiency of the drug delivery.
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$a Gruzinov, Andrey $u European Molecular Biology Laboratory, Deutsches Elektronen-Synchrotron, Notkestr. 85, 22607 Hamburg, Germany.
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$a Zaborova, Olga V $u Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského sq. 2, 16206 Prague, Czech Republic. Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119991 Moscow, Russia.
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$a Velychkivska, Nadiia $u Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského sq. 2, 16206 Prague, Czech Republic.
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$a Vaněk, Ondřej $u Department of Biochemistry, Faculty of Science, Charles University, Hlavova 2030/8, 12840 Prague, Czech Republic.
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$a Chytil, Petr $u Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského sq. 2, 16206 Prague, Czech Republic.
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$a Zhang, Xiaohan $u Fachgebiet Physik weicher Materie, Physik-Department, Technische Universität München, James-Franck-Str. 1, 85748 Garching, Germany.
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$a Blanchet, Clement $u European Molecular Biology Laboratory, Deutsches Elektronen-Synchrotron, Notkestr. 85, 22607 Hamburg, Germany.
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$a Papadakis, Christine M $u Fachgebiet Physik weicher Materie, Physik-Department, Technische Universität München, James-Franck-Str. 1, 85748 Garching, Germany.
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$a Svergun, Dmitri I $u European Molecular Biology Laboratory, Deutsches Elektronen-Synchrotron, Notkestr. 85, 22607 Hamburg, Germany.
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$a Filippov, Sergey K $u Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
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