Fast and effective mitochondrial delivery of ω-Rhodamine-B-polysulfobetaine-PEG copolymers

Abstract Mitochondrial targeting and entry, two crucial steps in fighting severe diseases resulting from mitochondria dysfunction, pose important challenges in current nanomedicine. Cell-penetrating peptides or targeting groups, such as Rhodamine-B (Rho), are known to localize in mitochondria, but l...

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Autores principales:	Nobuyuki Morimoto, Riho Takei, Masaru Wakamura, Yoshifumi Oishi, Masafumi Nakayama, Makoto Suzuki, Masaya Yamamoto, Françoise M. Winnik
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7508bfef58484ee289753378a7db0968
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spelling	oai:doaj.org-article:7508bfef58484ee289753378a7db09682021-12-02T15:07:52ZFast and effective mitochondrial delivery of ω-Rhodamine-B-polysulfobetaine-PEG copolymers10.1038/s41598-018-19598-22045-2322https://doaj.org/article/7508bfef58484ee289753378a7db09682018-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-19598-2https://doaj.org/toc/2045-2322Abstract Mitochondrial targeting and entry, two crucial steps in fighting severe diseases resulting from mitochondria dysfunction, pose important challenges in current nanomedicine. Cell-penetrating peptides or targeting groups, such as Rhodamine-B (Rho), are known to localize in mitochondria, but little is known on how to enhance their effectiveness through structural properties of polymeric carriers. To address this issue, we prepared 8 copolymers of 3-dimethyl(methacryloyloxyethyl)ammonium propane sulfonate and poly(ethyleneglycol) methacrylate, p(DMAPS-ran-PEGMA) (molecular weight, 18.0 < M n < 74.0 kg/mol) with two different endgroups. We labeled them with Rho groups attached along the chain or on one of the two endgroups (α or ω). From studies by flow cytometry and confocal fluorescence microscopy of the copolymers internalization in HeLa cells in the absence and presence of pharmacological inhibitors, we established that the polymers cross the cell membrane foremost by translocation and also by endocytosis, primarily clathrin-dependent endocytosis. The most effective mitochondrial entry was achieved by copolymers of M n < 30.0 kg/mol, lightly grafted with PEG chains (< 5 mol %) labeled with Rho in the ω-position. Our findings may be generalized to the uptake and mitochondrial targeting of prodrugs and imaging agents with a similar polymeric scaffold.Nobuyuki MorimotoRiho TakeiMasaru WakamuraYoshifumi OishiMasafumi NakayamaMakoto SuzukiMasaya YamamotoFrançoise M. WinnikNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nobuyuki Morimoto Riho Takei Masaru Wakamura Yoshifumi Oishi Masafumi Nakayama Makoto Suzuki Masaya Yamamoto Françoise M. Winnik Fast and effective mitochondrial delivery of ω-Rhodamine-B-polysulfobetaine-PEG copolymers
description	Abstract Mitochondrial targeting and entry, two crucial steps in fighting severe diseases resulting from mitochondria dysfunction, pose important challenges in current nanomedicine. Cell-penetrating peptides or targeting groups, such as Rhodamine-B (Rho), are known to localize in mitochondria, but little is known on how to enhance their effectiveness through structural properties of polymeric carriers. To address this issue, we prepared 8 copolymers of 3-dimethyl(methacryloyloxyethyl)ammonium propane sulfonate and poly(ethyleneglycol) methacrylate, p(DMAPS-ran-PEGMA) (molecular weight, 18.0 < M n < 74.0 kg/mol) with two different endgroups. We labeled them with Rho groups attached along the chain or on one of the two endgroups (α or ω). From studies by flow cytometry and confocal fluorescence microscopy of the copolymers internalization in HeLa cells in the absence and presence of pharmacological inhibitors, we established that the polymers cross the cell membrane foremost by translocation and also by endocytosis, primarily clathrin-dependent endocytosis. The most effective mitochondrial entry was achieved by copolymers of M n < 30.0 kg/mol, lightly grafted with PEG chains (< 5 mol %) labeled with Rho in the ω-position. Our findings may be generalized to the uptake and mitochondrial targeting of prodrugs and imaging agents with a similar polymeric scaffold.
format	article
author	Nobuyuki Morimoto Riho Takei Masaru Wakamura Yoshifumi Oishi Masafumi Nakayama Makoto Suzuki Masaya Yamamoto Françoise M. Winnik
author_facet	Nobuyuki Morimoto Riho Takei Masaru Wakamura Yoshifumi Oishi Masafumi Nakayama Makoto Suzuki Masaya Yamamoto Françoise M. Winnik
author_sort	Nobuyuki Morimoto
title	Fast and effective mitochondrial delivery of ω-Rhodamine-B-polysulfobetaine-PEG copolymers
title_short	Fast and effective mitochondrial delivery of ω-Rhodamine-B-polysulfobetaine-PEG copolymers
title_full	Fast and effective mitochondrial delivery of ω-Rhodamine-B-polysulfobetaine-PEG copolymers
title_fullStr	Fast and effective mitochondrial delivery of ω-Rhodamine-B-polysulfobetaine-PEG copolymers
title_full_unstemmed	Fast and effective mitochondrial delivery of ω-Rhodamine-B-polysulfobetaine-PEG copolymers
title_sort	fast and effective mitochondrial delivery of ω-rhodamine-b-polysulfobetaine-peg copolymers
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/7508bfef58484ee289753378a7db0968
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Fast and effective mitochondrial delivery of ω-Rhodamine-B-polysulfobetaine-PEG copolymers

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