Development of Polymer-Lipid Hybrid Nanoparticles for Large-Sized Plasmid DNA Transfection

Maeki, Masatoshi; Uno, Shuya; Sugiura, Kaisei; Sato, Yusuke; Fujioka, Yoichiro; Ishida, Akihiko; Ohba, Yusuke; Harashima, Hideyoshi; Tokeshi, Manabu

Development of Polymer-Lipid Hybrid Nanoparticles for Large-Sized Plasmid DNA Transfection

Maeki, Masatoshi; Uno, Shuya; Sugiura, Kaisei et al.

ACS applied materials & interfaces, 2024, 16(2), 2110-2119

Permalink : https://hdl.handle.net/2115/93817

このアイテムのアクセス数:149件（2026-08-17 01:33 集計）

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アクセス権	open access
URI	https://hdl.handle.net/2115/93817
タイトル	Development of Polymer-Lipid Hybrid Nanoparticles for Large-Sized Plasmid DNA Transfection
著者	Maeki, Masatoshi ; Uno, Shuya ; Sugiura, Kaisei ; Sato, Yusuke ; Fujioka, Yoichiro ; Ishida, Akihiko ; Ohba, Yusuke ; Harashima, Hideyoshi ; Tokeshi, Manabu
e-Rad_Researcher 40744248 著者名 Maeki, Masatoshi
著者名 Uno, Shuya
著者名 Sugiura, Kaisei
e-Rad_Researcher 10735624 著者名 Sato, Yusuke
e-Rad_Researcher 70597492 著者名 Fujioka, Yoichiro
e-Rad_Researcher 20312382 著者名 Ishida, Akihiko
e-Rad_Researcher 30333503 著者名 Ohba, Yusuke
著者名 Harashima, Hideyoshi
e-Rad_Researcher 60311437 著者名 Tokeshi, Manabu
言語	英語
キーワード	lipid nanoparticles
	polymer-lipidhybrid nanoparticle
	large plasmid DNA transfection
	core-shell nanoparticle
	microfluidic device
発行日	2024-01-17
出版者	American Chemical Society
収録物名	ACS applied materials & interfaces
巻(号)	16(2)
ページ	2110-2119
抄録	RNA and DNA delivery technologies using lipid nanoparticles (LNPs) have advanced significantly, as demonstrated by their successful application in mRNA vaccines. To date, commercially available RNA therapeutics include Onpattro, a 21 bp siRNA, and mRNA vaccines comprising 4300 nucleotides for COVID-19. However, a significant challenge remains in achieving efficient transfection, as the size of the delivered RNA and DNA increases. In contrast to RNA transfection, plasmid DNA (pDNA) transfection requires multiple steps, including cellular uptake, endosomal escape, nuclear translocation, transcription, and translation. The low transfection efficiency of large pDNA is a critical limitation in the development of artificial cells and their cellular functionalization. Here, we introduce polymer-lipid hybrid nanoparticles designed for efficient, large-sized pDNA transfection. We demonstrated that LNPs loaded with positively charged pDNA-polycation core nanoparticles exhibited a 4-fold increase in transfection efficiency for 15 kbp pDNA compared with conventional LNPs, which encapsulate a negatively charged pDNA-polycation core. Based on assessments of the size and internal structure of the polymer-lipid nanoparticles as well as hemolysis and cellular uptake analysis, we propose a strategy to enhance large-sized pDNA transfection using LNPs. This approach holds promise for accelerating the in vivo delivery of large-sized pDNA and advancing the development of artificial cells.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS applied materials & interfaces, copyright © 2023 The Authors. Published by American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/articlesonrequest/AOR-KXCSMXHBWWTQRB2DJUJI.
PISSN	1944-8244
関連情報	PMID 38141015
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1021/acsami.3c14714