Preparation of siRNA–PLGA/Fabʹ–PLGA mixed micellar system with target cell-specific recognition

Abstract Small interfering RNAs (siRNAs) are susceptible to nucleases and degrade quickly in vivo. Moreover, siRNAs demonstrate poor cellular uptake and cannot cross the cell membrane because of its polyanionic characteristics. To overcome these challenges, an intelligent gene delivery system that p...

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Autores principales:	Mai Hazekawa, Takuya Nishinakagawa, Takeshi Mori, Miyako Yoshida, Takahiro Uchida, Daisuke Ishibashi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9b11b42a60154855a4a1652ebfdb9cd5
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spelling	oai:doaj.org-article:9b11b42a60154855a4a1652ebfdb9cd52021-12-02T18:51:52ZPreparation of siRNA–PLGA/Fabʹ–PLGA mixed micellar system with target cell-specific recognition10.1038/s41598-021-96245-32045-2322https://doaj.org/article/9b11b42a60154855a4a1652ebfdb9cd52021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96245-3https://doaj.org/toc/2045-2322Abstract Small interfering RNAs (siRNAs) are susceptible to nucleases and degrade quickly in vivo. Moreover, siRNAs demonstrate poor cellular uptake and cannot cross the cell membrane because of its polyanionic characteristics. To overcome these challenges, an intelligent gene delivery system that protects siRNAs from nucleases and facilitates siRNA cellular uptake is required. We previously reported the potential of siRNA-poly(d,l-lactic-co-glycolic acid; PLGA) micelles as an effective siRNA delivery tool in a murine peritoneal dissemination model by local injection. However, there was no effective formulation for siRNA delivery to target cells via intravenous injection. This study aimed to prepare siRNA–PLGA/Fabʹ–PLGA mixed micelles for siRNA delivery to target floating cells and evaluate its formulation in vitro. As the target siRNA protein in CEMx174, CyclinB1 levels were significantly reduced when siRNA–PLGA/Fabʹ–PLGA mixed micelles were added to cells compared with siRNA–PLGA micelles. siRNA–PLGA/Fabʹ–PLGA mixed micelles have high cell permeability and high target cell accumulation by endocytosis because flow cytometry detected labeling micelles in target cells. This study supports siRNA–PLGA/Fabʹ–PLGA mixed micelles as an effective siRNA delivery tool. This formulation can be administered systemically in dosage form against target cells, including cancer metastasis or blood cancer.Mai HazekawaTakuya NishinakagawaTakeshi MoriMiyako YoshidaTakahiro UchidaDaisuke IshibashiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mai Hazekawa Takuya Nishinakagawa Takeshi Mori Miyako Yoshida Takahiro Uchida Daisuke Ishibashi Preparation of siRNA–PLGA/Fabʹ–PLGA mixed micellar system with target cell-specific recognition
description	Abstract Small interfering RNAs (siRNAs) are susceptible to nucleases and degrade quickly in vivo. Moreover, siRNAs demonstrate poor cellular uptake and cannot cross the cell membrane because of its polyanionic characteristics. To overcome these challenges, an intelligent gene delivery system that protects siRNAs from nucleases and facilitates siRNA cellular uptake is required. We previously reported the potential of siRNA-poly(d,l-lactic-co-glycolic acid; PLGA) micelles as an effective siRNA delivery tool in a murine peritoneal dissemination model by local injection. However, there was no effective formulation for siRNA delivery to target cells via intravenous injection. This study aimed to prepare siRNA–PLGA/Fabʹ–PLGA mixed micelles for siRNA delivery to target floating cells and evaluate its formulation in vitro. As the target siRNA protein in CEMx174, CyclinB1 levels were significantly reduced when siRNA–PLGA/Fabʹ–PLGA mixed micelles were added to cells compared with siRNA–PLGA micelles. siRNA–PLGA/Fabʹ–PLGA mixed micelles have high cell permeability and high target cell accumulation by endocytosis because flow cytometry detected labeling micelles in target cells. This study supports siRNA–PLGA/Fabʹ–PLGA mixed micelles as an effective siRNA delivery tool. This formulation can be administered systemically in dosage form against target cells, including cancer metastasis or blood cancer.
format	article
author	Mai Hazekawa Takuya Nishinakagawa Takeshi Mori Miyako Yoshida Takahiro Uchida Daisuke Ishibashi
author_facet	Mai Hazekawa Takuya Nishinakagawa Takeshi Mori Miyako Yoshida Takahiro Uchida Daisuke Ishibashi
author_sort	Mai Hazekawa
title	Preparation of siRNA–PLGA/Fabʹ–PLGA mixed micellar system with target cell-specific recognition
title_short	Preparation of siRNA–PLGA/Fabʹ–PLGA mixed micellar system with target cell-specific recognition
title_full	Preparation of siRNA–PLGA/Fabʹ–PLGA mixed micellar system with target cell-specific recognition
title_fullStr	Preparation of siRNA–PLGA/Fabʹ–PLGA mixed micellar system with target cell-specific recognition
title_full_unstemmed	Preparation of siRNA–PLGA/Fabʹ–PLGA mixed micellar system with target cell-specific recognition
title_sort	preparation of sirna–plga/fabʹ–plga mixed micellar system with target cell-specific recognition
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9b11b42a60154855a4a1652ebfdb9cd5
work_keys_str_mv	AT maihazekawa preparationofsirnaplgafabʹplgamixedmicellarsystemwithtargetcellspecificrecognition AT takuyanishinakagawa preparationofsirnaplgafabʹplgamixedmicellarsystemwithtargetcellspecificrecognition AT takeshimori preparationofsirnaplgafabʹplgamixedmicellarsystemwithtargetcellspecificrecognition AT miyakoyoshida preparationofsirnaplgafabʹplgamixedmicellarsystemwithtargetcellspecificrecognition AT takahirouchida preparationofsirnaplgafabʹplgamixedmicellarsystemwithtargetcellspecificrecognition AT daisukeishibashi preparationofsirnaplgafabʹplgamixedmicellarsystemwithtargetcellspecificrecognition
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Preparation of siRNA–PLGA/Fabʹ–PLGA mixed micellar system with target cell-specific recognition

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