Design of Oligonucleotide Carriers: Importance of Polyamine Chain Length.

Autor: Annenkov VV; Limnological Institute of the Siberian Branch of the Russian Academy of Sciences, 3, Ulan-Batorskaya St., P.O. Box 278, Irkutsk 664033, Russia. annenkov@lin.irk.ru., Krishnan UM; Centre for Nanotechnology & Advanced Biomaterials (CeNTAB), School of Chemical and Biotechnology, SASTRA University, Thanjavur 613401, Tamil Nadu, India. umakrishnan@sastra.edu., Pal'shin VA; Limnological Institute of the Siberian Branch of the Russian Academy of Sciences, 3, Ulan-Batorskaya St., P.O. Box 278, Irkutsk 664033, Russia. acrom@mail.ru., Zelinskiy SN; Limnological Institute of the Siberian Branch of the Russian Academy of Sciences, 3, Ulan-Batorskaya St., P.O. Box 278, Irkutsk 664033, Russia. jt1233@mail.ru., Kandasamy G; Centre for Nanotechnology & Advanced Biomaterials (CeNTAB), School of Chemical and Biotechnology, SASTRA University, Thanjavur 613401, Tamil Nadu, India. gayathri.ks86@gmail.com., Danilovtseva EN; Limnological Institute of the Siberian Branch of the Russian Academy of Sciences, 3, Ulan-Batorskaya St., P.O. Box 278, Irkutsk 664033, Russia. danilovtseva@yahoo.com.
Jazyk: angličtina
Zdroj: Polymers [Polymers (Basel)] 2018 Nov 23; Vol. 10 (12). Date of Electronic Publication: 2018 Nov 23.
DOI: 10.3390/polym10121297
Abstrakt: Amine containing polymers are extensively studied as special carriers for short-chain RNA (13⁻25 nucleotides), which are applied as gene silencing agents in gene therapy of various diseases including cancer. Elaboration of the oligonucleotide carriers requires knowledge about peculiarities of the oligonucleotide⁻polymeric amine interaction. The critical length of the interacting chains is an important parameter which allows us to design sophisticated constructions containing oligonucleotide binding segments, solubilizing, protective and aiming parts. We studied interactions of (TCAG)n, n = 1⁻6 DNA oligonucleotides with polyethylenimine and poly( N -(3-((3-(dimethylamino)propyl)(methyl)amino)propyl)- N -methylacrylamide). The critical length for oligonucleotides in interaction with polymeric amines is 8⁻12 units and complexation at these length can be accompanied by "all-or-nothing" effects. New dimethylacrylamide based polymers with grafted polyamine chains were obtained and studied in complexation with DNA and RNA oligonucleotides. The most effective interaction and transfection activity into A549 cancer cells and silencing efficiency against vascular endothelial growth factor (VEGF) was found for a sample with average number of nitrogens in polyamine chain equal to 27, i.e., for a sample in which all grafted chains are longer than the critical length for polymeric amine⁻oligonucleotide complexation.
Databáze: MEDLINE
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