Veronika Oravczova, Peter Bartek, Maria Bryszewska, Dzmitry Shcharbin, Zuzana Garaiova, Iveta Waczulíková, Maksim Ionov, Jean-Pierre Majoral, Zuzana Simonikova, Xiangyang Shi, Veronika Subjakova, Milan Zvarík, Simon Suty, Tibor Hianik, Serge Mignani, Comenius University in Bratislava, Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, University of Lódź, Institute of Biophysics and Cell Engineering, NASB, Minsk, National Academy of Sciences of Belarus (NASB), St. Elizabeth Cancer Institute, Centro de Química da Madeira, Universidade da Madeira (UMA), College of Chemistry, Chemical Engineering and Biotechnology, Donghua University (CCEB), Donghua University [Shanghai], Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), NAWA International Academic Partnership Programme EUROPARTNER, PPI/APM/2018/1/00007/U/001, University of Lodz, Slovak Research and Development Agency (APVV), Project Nos. SK-BY-RD-19-0019 and SK-PL-18-0080, State Committee on Science and Technology of the Republic of Belarus (SCST RB) B20-SLKG-002, Scientific Grant Agency of the Ministry of Education, Science, Research, and Sport of the Slovak Republic (VEGA), Project Nos. 1/0756/20 and 01/0136/18, Cultural and Educational Grant Agency of the Ministry of Education, Science, Research, and Sport of the Slovak Republic (KEGA) 041UK-4/2020, and Comenius University
International audience; Dendrons are branched synthetic polymers suitable for preparation of nanosized drug delivery systems. Their interactions with biological systems are mainly predetermined by their chemical structure, terminal groups, surface charge, and the number of branched layers (generation). Any new compound intended to be used, alone or in combination, for medical purposes in humans must be compatible with blood. This study combined results from in vitro experiments on human blood and from laboratory experiments designed to assess the effect of amphiphilic phosphorous dendrons on blood components and model membranes, and to examine the presence and nature of interactions leading to a potential safety concern. The changes in hematological and coagulation parameters upon the addition of dendrons in the concentration range of 2–10 µM were monitored. We found that only the combination of higher concentration and higher generation of the dendron affected the selected clinically relevant parameters: it significantly decreased platelet count and plateletcrit, shortened thrombin time, and increased activated partial thromboplastin time. At the same time, occasional small-sized platelet clumps in blood films under the light microscope were observed. We further investigated aggregation propensity of the positively charged dendrons in model conditions using zwitterionic and negatively charged liposomes. The observed changes in size and zeta potential indicated the electrostatic nature of the interaction. Overall, we proved that the low-generation amphiphilic phosphorous dendrons were compatible with blood within the studied concentration range. However, interactions between high-generation dendrons at bulk concentrations above 10 µM and platelets and/or clotting factors cannot be excluded.