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The Formation of Nanoparticles between Small Interfering RNA and Amphipathic Cell-Penetrating Peptides

Cell-penetrating peptides (CPPs) are delivery vectors widely used to aid the transport of biologically active cargoes to intracellular targets. These cargoes include small interfering RNAs (siRNA) that are not naturally internalized by cells. Elucidating the complexities behind the formation of CPP...

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Detalles Bibliográficos
Autores principales: Pärnaste, Ly, Arukuusk, Piret, Langel, Kent, Tenson, Tanel, Langel, Ülo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363680/
https://www.ncbi.nlm.nih.gov/pubmed/28624185
http://dx.doi.org/10.1016/j.omtn.2017.02.003
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author Pärnaste, Ly
Arukuusk, Piret
Langel, Kent
Tenson, Tanel
Langel, Ülo
author_facet Pärnaste, Ly
Arukuusk, Piret
Langel, Kent
Tenson, Tanel
Langel, Ülo
author_sort Pärnaste, Ly
collection PubMed
description Cell-penetrating peptides (CPPs) are delivery vectors widely used to aid the transport of biologically active cargoes to intracellular targets. These cargoes include small interfering RNAs (siRNA) that are not naturally internalized by cells. Elucidating the complexities behind the formation of CPP and cargo complexes is crucial for understanding the processes related to their delivery. In this study, we used modified analogs of the CPP transportan10 and investigated the binding properties of these CPPs to siRNA, the formation parameters of the CPP/siRNA complexes, and their stabiliy to enzymatic degradation. We conclude that the pH dependent change of the net charge of the CPP may very well be the key factor leading to the high delivery efficiency and the optimal binding strength between CPPs to siRNAs, while the hydrophobicity, secondary structure of the CPP, and the positions of the positive charges are responsible for the stability of the CPP/siRNA particles. Also, CPPs with distinct hydrophobic and hydrophilic regions may assemble into nanoparticles that could be described as core-shell formulations.
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spelling pubmed-53636802017-03-24 The Formation of Nanoparticles between Small Interfering RNA and Amphipathic Cell-Penetrating Peptides Pärnaste, Ly Arukuusk, Piret Langel, Kent Tenson, Tanel Langel, Ülo Mol Ther Nucleic Acids Original Article Cell-penetrating peptides (CPPs) are delivery vectors widely used to aid the transport of biologically active cargoes to intracellular targets. These cargoes include small interfering RNAs (siRNA) that are not naturally internalized by cells. Elucidating the complexities behind the formation of CPP and cargo complexes is crucial for understanding the processes related to their delivery. In this study, we used modified analogs of the CPP transportan10 and investigated the binding properties of these CPPs to siRNA, the formation parameters of the CPP/siRNA complexes, and their stabiliy to enzymatic degradation. We conclude that the pH dependent change of the net charge of the CPP may very well be the key factor leading to the high delivery efficiency and the optimal binding strength between CPPs to siRNAs, while the hydrophobicity, secondary structure of the CPP, and the positions of the positive charges are responsible for the stability of the CPP/siRNA particles. Also, CPPs with distinct hydrophobic and hydrophilic regions may assemble into nanoparticles that could be described as core-shell formulations. American Society of Gene & Cell Therapy 2017-06-16 2017-02-10 /pmc/articles/PMC5363680/ /pubmed/28624185 http://dx.doi.org/10.1016/j.omtn.2017.02.003 Text en © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Pärnaste, Ly
Arukuusk, Piret
Langel, Kent
Tenson, Tanel
Langel, Ülo
The Formation of Nanoparticles between Small Interfering RNA and Amphipathic Cell-Penetrating Peptides
title The Formation of Nanoparticles between Small Interfering RNA and Amphipathic Cell-Penetrating Peptides
title_full The Formation of Nanoparticles between Small Interfering RNA and Amphipathic Cell-Penetrating Peptides
title_fullStr The Formation of Nanoparticles between Small Interfering RNA and Amphipathic Cell-Penetrating Peptides
title_full_unstemmed The Formation of Nanoparticles between Small Interfering RNA and Amphipathic Cell-Penetrating Peptides
title_short The Formation of Nanoparticles between Small Interfering RNA and Amphipathic Cell-Penetrating Peptides
title_sort formation of nanoparticles between small interfering rna and amphipathic cell-penetrating peptides
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363680/
https://www.ncbi.nlm.nih.gov/pubmed/28624185
http://dx.doi.org/10.1016/j.omtn.2017.02.003
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