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Effect of Polymer Phase Transition Behavior on Temperature-Responsive Polymer-Modified Liposomes for siRNA Transfection

Small interfering RNAs (siRNAs) have been attracting significant attention owing to their gene silencing properties, which can be utilized to treat intractable diseases. In this study, two temperature-responsive liposomal siRNA carriers were prepared by modifying liposomes with different polymers—po...

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Autores principales: Nagase, Kenichi, Hasegawa, Momoko, Ayano, Eri, Maitani, Yoshie, Kanazawa, Hideko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358841/
https://www.ncbi.nlm.nih.gov/pubmed/30669495
http://dx.doi.org/10.3390/ijms20020430
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author Nagase, Kenichi
Hasegawa, Momoko
Ayano, Eri
Maitani, Yoshie
Kanazawa, Hideko
author_facet Nagase, Kenichi
Hasegawa, Momoko
Ayano, Eri
Maitani, Yoshie
Kanazawa, Hideko
author_sort Nagase, Kenichi
collection PubMed
description Small interfering RNAs (siRNAs) have been attracting significant attention owing to their gene silencing properties, which can be utilized to treat intractable diseases. In this study, two temperature-responsive liposomal siRNA carriers were prepared by modifying liposomes with different polymers—poly(N-isopropylacrylamide-co-N,N-dimethylaminopropyl acrylamide) (P(NIPAAm-co-DMAPAAm)) and poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) P(NIPAAm-co-DMAAm). The phase transition of P(NIPAAm-co-DMAPAAm) was sharper than that of P(NIPAAm-co-DMAAm), which is attributed to the lower co-monomer content. The temperature dependent fixed aqueous layer thickness (FALT) of the prepared liposomes indicated that modifying liposomes with P(NIPAAm-co-DMAPAAm) led to a significant change in the thickness of the fixed aqueous monolayer between 37 °C and 42 °C; while P(NIPAAm-co-DMAAm) modification led to FALT changes over a broader temperature range. The temperature-responsive liposomes exhibited cellular uptake at 42 °C, but were not taken up by cells at 37 °C. This is likely because the thermoresponsive hydrophilic/hydrophobic changes at the liposome surface induced temperature-responsive cellular uptake. Additionally, siRNA transfection of cells for the prevention of luciferase and vascular endothelial growth factor (VEGF) expression was modulated by external temperature changes. P(NIPAAm-co-DMAPAAm) modified liposomes in particular exhibited effective siRNA transfection properties with low cytotoxicity compared with P(NIPAAm-co-DMAAm) modified analogues. These results indicated that the prepared temperature-responsive liposomes could be used as effective siRNA carriers whose transfection properties can be modulated by temperature.
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spelling pubmed-63588412019-02-06 Effect of Polymer Phase Transition Behavior on Temperature-Responsive Polymer-Modified Liposomes for siRNA Transfection Nagase, Kenichi Hasegawa, Momoko Ayano, Eri Maitani, Yoshie Kanazawa, Hideko Int J Mol Sci Article Small interfering RNAs (siRNAs) have been attracting significant attention owing to their gene silencing properties, which can be utilized to treat intractable diseases. In this study, two temperature-responsive liposomal siRNA carriers were prepared by modifying liposomes with different polymers—poly(N-isopropylacrylamide-co-N,N-dimethylaminopropyl acrylamide) (P(NIPAAm-co-DMAPAAm)) and poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) P(NIPAAm-co-DMAAm). The phase transition of P(NIPAAm-co-DMAPAAm) was sharper than that of P(NIPAAm-co-DMAAm), which is attributed to the lower co-monomer content. The temperature dependent fixed aqueous layer thickness (FALT) of the prepared liposomes indicated that modifying liposomes with P(NIPAAm-co-DMAPAAm) led to a significant change in the thickness of the fixed aqueous monolayer between 37 °C and 42 °C; while P(NIPAAm-co-DMAAm) modification led to FALT changes over a broader temperature range. The temperature-responsive liposomes exhibited cellular uptake at 42 °C, but were not taken up by cells at 37 °C. This is likely because the thermoresponsive hydrophilic/hydrophobic changes at the liposome surface induced temperature-responsive cellular uptake. Additionally, siRNA transfection of cells for the prevention of luciferase and vascular endothelial growth factor (VEGF) expression was modulated by external temperature changes. P(NIPAAm-co-DMAPAAm) modified liposomes in particular exhibited effective siRNA transfection properties with low cytotoxicity compared with P(NIPAAm-co-DMAAm) modified analogues. These results indicated that the prepared temperature-responsive liposomes could be used as effective siRNA carriers whose transfection properties can be modulated by temperature. MDPI 2019-01-19 /pmc/articles/PMC6358841/ /pubmed/30669495 http://dx.doi.org/10.3390/ijms20020430 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nagase, Kenichi
Hasegawa, Momoko
Ayano, Eri
Maitani, Yoshie
Kanazawa, Hideko
Effect of Polymer Phase Transition Behavior on Temperature-Responsive Polymer-Modified Liposomes for siRNA Transfection
title Effect of Polymer Phase Transition Behavior on Temperature-Responsive Polymer-Modified Liposomes for siRNA Transfection
title_full Effect of Polymer Phase Transition Behavior on Temperature-Responsive Polymer-Modified Liposomes for siRNA Transfection
title_fullStr Effect of Polymer Phase Transition Behavior on Temperature-Responsive Polymer-Modified Liposomes for siRNA Transfection
title_full_unstemmed Effect of Polymer Phase Transition Behavior on Temperature-Responsive Polymer-Modified Liposomes for siRNA Transfection
title_short Effect of Polymer Phase Transition Behavior on Temperature-Responsive Polymer-Modified Liposomes for siRNA Transfection
title_sort effect of polymer phase transition behavior on temperature-responsive polymer-modified liposomes for sirna transfection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358841/
https://www.ncbi.nlm.nih.gov/pubmed/30669495
http://dx.doi.org/10.3390/ijms20020430
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