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Amphiphilic Polypeptides for VEGF siRNA Delivery into Retinal Epithelial Cells. / Osipova, Olga ; Sharoyko, Vladimir ; Zashikhina, Natalia ; Zakharova, Natalya ; Tennikova , Tatiana ; Urtti, Arto ; Korzhikova-Vlakh, Evgenia .

In: Pharmaceutics, Vol. 12, No. 1, 39, 01.2020.

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@article{606b6ff2387a4929bdfdc4b4d23b51f0,
title = "Amphiphilic Polypeptides for VEGF siRNA Delivery into Retinal Epithelial Cells",
abstract = "Polyethyleneimine, poly-L-lysine, chitosan and some others cationic polymers have been thoroughly studied as nucleic acid delivery systems in gene therapy. However, the drug release from these systems proceeds at a very low rate due to extremely high binding between a carrier and gene material. To reduce these interactions and to enhance drug release, we developed a set of amphiphilic polypeptides containing positively and negatively charged amino acids as well as a hydrophobic one. The copolymers obtained were characterized by size-exclusion chromatography, static light scattering, HPLC amino acid analysis and 1HNMR spectroscopy. All copolymers formed particles due to a self-assembly in aqueous media. Depending on polypeptide composition, the formation of particles with hydrodynamic diameters from 180 to 900 nm was observed. Stability of polymer particles, loading and release efficiency were carefully studied. Cellular uptake of the particles was efficient and their cytotoxicity was negligible. The application of polymer carriers, containing siRNA, to vascular endothelial growth factor (VEGF-A165) silencing of ARPE-19 cells was successful. The gene silencing was confirmed by suppression of both messenger RNA and protein expression.",
keywords = "Amphiphilic polypeptides, Gene silencing, Nanoparticles, Self-assembly, VEGF, siRNA delivery",
author = "Olga Osipova and Vladimir Sharoyko and Natalia Zashikhina and Natalya Zakharova and Tatiana Tennikova and Arto Urtti and Evgenia Korzhikova-Vlakh",
note = "Funding Information: Funding: The financial support was provided by Government of Russian Federation (Megagrant #14.W03.31.0025).",
year = "2020",
month = jan,
doi = "10.3390/pharmaceutics12010039",
language = "English",
volume = "12",
journal = "Pharmaceutics",
issn = "1999-4923",
publisher = "MDPI AG",
number = "1",

}

RIS

TY - JOUR

T1 - Amphiphilic Polypeptides for VEGF siRNA Delivery into Retinal Epithelial Cells

AU - Osipova, Olga

AU - Sharoyko, Vladimir

AU - Zashikhina, Natalia

AU - Zakharova, Natalya

AU - Tennikova , Tatiana

AU - Urtti, Arto

AU - Korzhikova-Vlakh, Evgenia

N1 - Funding Information: Funding: The financial support was provided by Government of Russian Federation (Megagrant #14.W03.31.0025).

PY - 2020/1

Y1 - 2020/1

N2 - Polyethyleneimine, poly-L-lysine, chitosan and some others cationic polymers have been thoroughly studied as nucleic acid delivery systems in gene therapy. However, the drug release from these systems proceeds at a very low rate due to extremely high binding between a carrier and gene material. To reduce these interactions and to enhance drug release, we developed a set of amphiphilic polypeptides containing positively and negatively charged amino acids as well as a hydrophobic one. The copolymers obtained were characterized by size-exclusion chromatography, static light scattering, HPLC amino acid analysis and 1HNMR spectroscopy. All copolymers formed particles due to a self-assembly in aqueous media. Depending on polypeptide composition, the formation of particles with hydrodynamic diameters from 180 to 900 nm was observed. Stability of polymer particles, loading and release efficiency were carefully studied. Cellular uptake of the particles was efficient and their cytotoxicity was negligible. The application of polymer carriers, containing siRNA, to vascular endothelial growth factor (VEGF-A165) silencing of ARPE-19 cells was successful. The gene silencing was confirmed by suppression of both messenger RNA and protein expression.

AB - Polyethyleneimine, poly-L-lysine, chitosan and some others cationic polymers have been thoroughly studied as nucleic acid delivery systems in gene therapy. However, the drug release from these systems proceeds at a very low rate due to extremely high binding between a carrier and gene material. To reduce these interactions and to enhance drug release, we developed a set of amphiphilic polypeptides containing positively and negatively charged amino acids as well as a hydrophobic one. The copolymers obtained were characterized by size-exclusion chromatography, static light scattering, HPLC amino acid analysis and 1HNMR spectroscopy. All copolymers formed particles due to a self-assembly in aqueous media. Depending on polypeptide composition, the formation of particles with hydrodynamic diameters from 180 to 900 nm was observed. Stability of polymer particles, loading and release efficiency were carefully studied. Cellular uptake of the particles was efficient and their cytotoxicity was negligible. The application of polymer carriers, containing siRNA, to vascular endothelial growth factor (VEGF-A165) silencing of ARPE-19 cells was successful. The gene silencing was confirmed by suppression of both messenger RNA and protein expression.

KW - Amphiphilic polypeptides

KW - Gene silencing

KW - Nanoparticles

KW - Self-assembly

KW - VEGF

KW - siRNA delivery

UR - http://www.scopus.com/inward/record.url?scp=85078562232&partnerID=8YFLogxK

U2 - 10.3390/pharmaceutics12010039

DO - 10.3390/pharmaceutics12010039

M3 - Article

VL - 12

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 1

M1 - 39

ER -

ID: 61444572