Application of new lysine-based peptide dendrimers D3K2 and D3G2 for gene delivery: Specific cytotoxicity to cancer cells and transfection in vitro.

Autor:	Gorzkiewicz M; Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland., Konopka M; Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland., Janaszewska A; Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland., Tarasenko II; Institute of Macromolecular Compounds, Russian Academy of Sciences, Bolshoi Prospect 31, V.O., St. Petersburg 199004, Russia., Sheveleva NN; St. Petersburg State University, 7/9 Universitetskaya nab., St. Petersburg 199034, Russia; Laboratory of Physics, Lappeenranta University of Technology, Box 20, 53851 Lappeenranta, Finland., Gajek A; Department of Medical Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland., Neelov IM; St. Petersburg National Research University of Information Technologies, Mechanics and Optics (ITMO University), Kronverkskiy pr. 49, St. Petersburg 197101, Russia., Klajnert-Maculewicz B; Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland; Leibniz-Institut für Polymerforschung Dresden e.V., 6 Hohe St., 01069 Dresden, Germany. Electronic address: barbara.klajnert@biol.uni.lodz.pl.
Jazyk:	angličtina
Zdroj:	Bioorganic chemistry [Bioorg Chem] 2020 Jan; Vol. 95, pp. 103504. Date of Electronic Publication: 2019 Dec 11.
DOI:	10.1016/j.bioorg.2019.103504
Abstrakt:	In order to enhance intracellular uptake and accumulation of therapeutic nucleic acids for improved gene therapy methods, numerous delivery vectors have been elaborated. Based on their origin, gene carriers are generally classified as viral or non-viral vectors. Due to their significantly reduced immunogenicity and highly optimized methods of synthesis, nanoparticles (especially those imitating natural biomolecules) constitute a promising alternative for virus-based delivery devices. Thus, we set out to develop innovative peptide dendrimers for clinical application as transfection agents and gene carriers. In the present work we describe the synthesis of two novel lysine-based dendritic macromolecules (D3K2 and D3G2) and their initial characterization for cytotoxicity/genotoxicity and transfection potential in two human cell line models: cervix adenocarcinoma (HeLa) and microvascular endothelial (HMEC-1). This approach allowed us to identify more cationic D3K2 as potent delivery agent, being able to increase intracellular accumulation of large nucleic acid molecules such as plasmids. Moreover, the dendrimers exhibited specific cytotoxicity towards cancer cell line without showing significant toxic effects on normal cells. These observations are promising prognosis for future clinical application of this type of nanoparticles. (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Full Text from ScienceDirect