Cytosolic protein delivery using pH-responsive, charge-reversible lipid nanoparticles

Abstract Although proteins have attractive features as biopharmaceuticals, the difficulty in delivering them into the cell interior limits their applicability. Lipid nanoparticles (LNPs) are a promising class of delivery vehicles. When designing a protein delivery system based on LNPs, the major cha...

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Autores principales:	Yusuke Hirai, Hisaaki Hirose, Miki Imanishi, Tomohiro Asai, Shiroh Futaki
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5b79394d705e4bc08ba13993b49b0bac
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spelling	oai:doaj.org-article:5b79394d705e4bc08ba13993b49b0bac2021-12-02T19:16:11ZCytosolic protein delivery using pH-responsive, charge-reversible lipid nanoparticles10.1038/s41598-021-99180-52045-2322https://doaj.org/article/5b79394d705e4bc08ba13993b49b0bac2021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99180-5https://doaj.org/toc/2045-2322Abstract Although proteins have attractive features as biopharmaceuticals, the difficulty in delivering them into the cell interior limits their applicability. Lipid nanoparticles (LNPs) are a promising class of delivery vehicles. When designing a protein delivery system based on LNPs, the major challenges include: (i) formulation of LNPs with defined particle sizes and dispersity, (ii) efficient encapsulation of cargo proteins into LNPs, and (iii) effective cellular uptake and endosomal release into the cytosol. Dioleoylglycerophosphate-diethylenediamine (DOP-DEDA) is a pH-responsive, charge-reversible lipid. The aim of this study was to evaluate the applicability of DOP-DEDA-based LNPs for intracellular protein delivery. Considering the importance of electrostatic interactions in protein encapsulation into LNPs, a negatively charged green fluorescent protein (GFP) analog was successfully encapsulated into DOP-DEDA-based LNPs to yield diameters and polydispersity index of < 200 nm and < 0.2, respectively. Moreover, ~ 80% of the cargo proteins was encapsulated into the LNPs. Cytosolic distribution of fluorescent signals of the protein was observed for up to ~ 90% cells treated with the LNPs, indicating the facilitated endocytic uptake and endosomal escape of the cargo attained using the LNP system.Yusuke HiraiHisaaki HiroseMiki ImanishiTomohiro AsaiShiroh FutakiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yusuke Hirai Hisaaki Hirose Miki Imanishi Tomohiro Asai Shiroh Futaki Cytosolic protein delivery using pH-responsive, charge-reversible lipid nanoparticles
description	Abstract Although proteins have attractive features as biopharmaceuticals, the difficulty in delivering them into the cell interior limits their applicability. Lipid nanoparticles (LNPs) are a promising class of delivery vehicles. When designing a protein delivery system based on LNPs, the major challenges include: (i) formulation of LNPs with defined particle sizes and dispersity, (ii) efficient encapsulation of cargo proteins into LNPs, and (iii) effective cellular uptake and endosomal release into the cytosol. Dioleoylglycerophosphate-diethylenediamine (DOP-DEDA) is a pH-responsive, charge-reversible lipid. The aim of this study was to evaluate the applicability of DOP-DEDA-based LNPs for intracellular protein delivery. Considering the importance of electrostatic interactions in protein encapsulation into LNPs, a negatively charged green fluorescent protein (GFP) analog was successfully encapsulated into DOP-DEDA-based LNPs to yield diameters and polydispersity index of < 200 nm and < 0.2, respectively. Moreover, ~ 80% of the cargo proteins was encapsulated into the LNPs. Cytosolic distribution of fluorescent signals of the protein was observed for up to ~ 90% cells treated with the LNPs, indicating the facilitated endocytic uptake and endosomal escape of the cargo attained using the LNP system.
format	article
author	Yusuke Hirai Hisaaki Hirose Miki Imanishi Tomohiro Asai Shiroh Futaki
author_facet	Yusuke Hirai Hisaaki Hirose Miki Imanishi Tomohiro Asai Shiroh Futaki
author_sort	Yusuke Hirai
title	Cytosolic protein delivery using pH-responsive, charge-reversible lipid nanoparticles
title_short	Cytosolic protein delivery using pH-responsive, charge-reversible lipid nanoparticles
title_full	Cytosolic protein delivery using pH-responsive, charge-reversible lipid nanoparticles
title_fullStr	Cytosolic protein delivery using pH-responsive, charge-reversible lipid nanoparticles
title_full_unstemmed	Cytosolic protein delivery using pH-responsive, charge-reversible lipid nanoparticles
title_sort	cytosolic protein delivery using ph-responsive, charge-reversible lipid nanoparticles
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5b79394d705e4bc08ba13993b49b0bac
work_keys_str_mv	AT yusukehirai cytosolicproteindeliveryusingphresponsivechargereversiblelipidnanoparticles AT hisaakihirose cytosolicproteindeliveryusingphresponsivechargereversiblelipidnanoparticles AT mikiimanishi cytosolicproteindeliveryusingphresponsivechargereversiblelipidnanoparticles AT tomohiroasai cytosolicproteindeliveryusingphresponsivechargereversiblelipidnanoparticles AT shirohfutaki cytosolicproteindeliveryusingphresponsivechargereversiblelipidnanoparticles
_version_	1718376972532318208

Cytosolic protein delivery using pH-responsive, charge-reversible lipid nanoparticles

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