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Article

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

1
Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského sq. 2, 16206 Prague, Czech Republic
2
European Molecular Biology Laboratory, Deutsches Elektronen-Synchrotron, Notkestr. 85, 22607 Hamburg, Germany
3
Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119991 Moscow, Russia
4
Department of Biochemistry, Faculty of Science, Charles University, Hlavova 2030/8, 12840 Prague, Czech Republic
5
Fachgebiet Physik weicher Materie, Physik-Department, Technische Universität München, James-Franck-Str. 1, 85748 Garching, Germany
6
Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(2), 106; https://doi.org/10.3390/pharmaceutics12020106
Received: 20 November 2019 / Revised: 14 January 2020 / Accepted: 26 January 2020 / Published: 28 January 2020
(This article belongs to the Special Issue Advanced Polymeric Delivery Systems for Cancer Therapy)
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. View Full-Text
Keywords: drug delivery; pHPMA; plasma proteins; polymeric nanoparticles; stealth effect drug delivery; pHPMA; plasma proteins; polymeric nanoparticles; stealth effect
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MDPI and ACS Style

Janisova, L.; Gruzinov, A.; Zaborova, O.V.; Velychkivska, N.; Vaněk, O.; Chytil, P.; Etrych, T.; Janoušková, O.; Zhang, X.; Blanchet, C.; Papadakis, C.M.; Svergun, D.I.; Filippov, S.K. Molecular Mechanisms of the Interactions of N-(2-Hydroxypropyl)methacrylamide Copolymers Designed for Cancer Therapy with Blood Plasma Proteins. Pharmaceutics 2020, 12, 106. https://doi.org/10.3390/pharmaceutics12020106

AMA Style

Janisova L, Gruzinov A, Zaborova OV, Velychkivska N, Vaněk O, Chytil P, Etrych T, Janoušková O, Zhang X, Blanchet C, Papadakis CM, Svergun DI, Filippov SK. Molecular Mechanisms of the Interactions of N-(2-Hydroxypropyl)methacrylamide Copolymers Designed for Cancer Therapy with Blood Plasma Proteins. Pharmaceutics. 2020; 12(2):106. https://doi.org/10.3390/pharmaceutics12020106

Chicago/Turabian Style

Janisova, Larisa, Andrey Gruzinov, Olga V. Zaborova, Nadiia Velychkivska, Ondřej Vaněk, Petr Chytil, Tomáš Etrych, Olga Janoušková, Xiaohan Zhang, Clement Blanchet, Christine M. Papadakis, Dmitri I. Svergun, and Sergey K. Filippov 2020. "Molecular Mechanisms of the Interactions of N-(2-Hydroxypropyl)methacrylamide Copolymers Designed for Cancer Therapy with Blood Plasma Proteins" Pharmaceutics 12, no. 2: 106. https://doi.org/10.3390/pharmaceutics12020106

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