Intracellular Distribution of Lipids and Encapsulated Model Drugs from Cationic Liposomes with Different Uptake Pathways

Masato Takikawa,1 Mizuki Fujisawa,2 Kazuma Yoshino,2 Shinji Takeoka2,3 1Department of Advanced Science and Engineering, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo 169-8555, Japan; 2Department of Life Science and Medical Bioscience, Graduate Schoolof Advanced Scienc...

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Autores principales:	Takikawa M, Fujisawa M, Yoshino K, Takeoka S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	cationic liposome amino lipid intracellular delivery endocytosis membrane fusion intracellular pharmacokinetics Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5bb311f7e17e4e038151561b63b90d81
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spelling	oai:doaj.org-article:5bb311f7e17e4e038151561b63b90d812021-12-02T12:42:06ZIntracellular Distribution of Lipids and Encapsulated Model Drugs from Cationic Liposomes with Different Uptake Pathways1178-2013https://doaj.org/article/5bb311f7e17e4e038151561b63b90d812020-10-01T00:00:00Zhttps://www.dovepress.com/intracellular-distribution-of-lipids-and-encapsulated-model-drugs-from-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Masato Takikawa,1 Mizuki Fujisawa,2 Kazuma Yoshino,2 Shinji Takeoka2,3 1Department of Advanced Science and Engineering, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo 169-8555, Japan; 2Department of Life Science and Medical Bioscience, Graduate Schoolof Advanced Science and Engineering, Waseda University (TWIns), Tokyo 162-8480, Japan; 3Institute for Advanced Research of Biosystem Dynamics, Waseda Research Institute for Science and Engineering, Waseda University, Tokyo 169-8555, JapanCorrespondence: Shinji TakeokaDepartment of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University (TWIns), Shinjuku-ku, Tokyo 162-8480, JapanTel +81-3-5369-7324Fax +81-5369-7324Email takeoka@waseda.jpAim: The uptake pathway of liposomes into cells is mainly via endocytosis or membrane fusion; however, the relationship between the uptake pathway and the intracellular pharmacokinetics of the liposome components remains unclear. This study aimed at revealing the relationship by using cationic liposomes having similar physical properties and different uptake pathways.Materials and Methods: We prepared cationic liposomes composed of amino acid-type lipids, K3C14 and K3C16, which have different uptake pathways by a hydration method, and fluorescently modified them by encapsulating FITC-dextran and surface conjugation with Alexa Fluor® 488 (AF488). Then, we investigated their intracellular distribution in HeLa cells over time.Results: The liposomes had similar physical properties and did not cause significant cell mortality after treatment for 180 min. The delivery rate and efficiency of encapsulated FITC-dextran with the fusogenic K3C16 liposomes were 3 and 1.6 times higher, respectively, than with the endocytic K3C14 liposomes. FITC-dextran molecules delivered with K3C16 liposomes were observed throughout the cytosolic space after 10 min, while those delivered with K3C14 liposomes were mainly observed as foci and took 60 min to diffuse into the cytosolic space. K3C14 lipids modified with AF488 were distributed mostly in the cytosolic space. In contrast, fluorescently labeled K3C16 lipids were colocalized with the plasma membrane of 50% of the HeLa cells after 10 min and were gradually internalized intracellularly.Conclusion: Fusogenic K3C16 liposomes internalized into HeLa cells faster than endocytic K3C14 liposomes, and their components differently distributed in the cells.Keywords: cationic liposome, amino lipid, intracellular delivery, endocytosis, membrane fusion, intracellular pharmacokineticsTakikawa MFujisawa MYoshino KTakeoka SDove Medical Pressarticlecationic liposomeamino lipidintracellular deliveryendocytosismembrane fusionintracellular pharmacokineticsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 8401-8409 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	cationic liposome amino lipid intracellular delivery endocytosis membrane fusion intracellular pharmacokinetics Medicine (General) R5-920
spellingShingle	cationic liposome amino lipid intracellular delivery endocytosis membrane fusion intracellular pharmacokinetics Medicine (General) R5-920 Takikawa M Fujisawa M Yoshino K Takeoka S Intracellular Distribution of Lipids and Encapsulated Model Drugs from Cationic Liposomes with Different Uptake Pathways
description	Masato Takikawa,1 Mizuki Fujisawa,2 Kazuma Yoshino,2 Shinji Takeoka2,3 1Department of Advanced Science and Engineering, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo 169-8555, Japan; 2Department of Life Science and Medical Bioscience, Graduate Schoolof Advanced Science and Engineering, Waseda University (TWIns), Tokyo 162-8480, Japan; 3Institute for Advanced Research of Biosystem Dynamics, Waseda Research Institute for Science and Engineering, Waseda University, Tokyo 169-8555, JapanCorrespondence: Shinji TakeokaDepartment of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University (TWIns), Shinjuku-ku, Tokyo 162-8480, JapanTel +81-3-5369-7324Fax +81-5369-7324Email takeoka@waseda.jpAim: The uptake pathway of liposomes into cells is mainly via endocytosis or membrane fusion; however, the relationship between the uptake pathway and the intracellular pharmacokinetics of the liposome components remains unclear. This study aimed at revealing the relationship by using cationic liposomes having similar physical properties and different uptake pathways.Materials and Methods: We prepared cationic liposomes composed of amino acid-type lipids, K3C14 and K3C16, which have different uptake pathways by a hydration method, and fluorescently modified them by encapsulating FITC-dextran and surface conjugation with Alexa Fluor® 488 (AF488). Then, we investigated their intracellular distribution in HeLa cells over time.Results: The liposomes had similar physical properties and did not cause significant cell mortality after treatment for 180 min. The delivery rate and efficiency of encapsulated FITC-dextran with the fusogenic K3C16 liposomes were 3 and 1.6 times higher, respectively, than with the endocytic K3C14 liposomes. FITC-dextran molecules delivered with K3C16 liposomes were observed throughout the cytosolic space after 10 min, while those delivered with K3C14 liposomes were mainly observed as foci and took 60 min to diffuse into the cytosolic space. K3C14 lipids modified with AF488 were distributed mostly in the cytosolic space. In contrast, fluorescently labeled K3C16 lipids were colocalized with the plasma membrane of 50% of the HeLa cells after 10 min and were gradually internalized intracellularly.Conclusion: Fusogenic K3C16 liposomes internalized into HeLa cells faster than endocytic K3C14 liposomes, and their components differently distributed in the cells.Keywords: cationic liposome, amino lipid, intracellular delivery, endocytosis, membrane fusion, intracellular pharmacokinetics
format	article
author	Takikawa M Fujisawa M Yoshino K Takeoka S
author_facet	Takikawa M Fujisawa M Yoshino K Takeoka S
author_sort	Takikawa M
title	Intracellular Distribution of Lipids and Encapsulated Model Drugs from Cationic Liposomes with Different Uptake Pathways
title_short	Intracellular Distribution of Lipids and Encapsulated Model Drugs from Cationic Liposomes with Different Uptake Pathways
title_full	Intracellular Distribution of Lipids and Encapsulated Model Drugs from Cationic Liposomes with Different Uptake Pathways
title_fullStr	Intracellular Distribution of Lipids and Encapsulated Model Drugs from Cationic Liposomes with Different Uptake Pathways
title_full_unstemmed	Intracellular Distribution of Lipids and Encapsulated Model Drugs from Cationic Liposomes with Different Uptake Pathways
title_sort	intracellular distribution of lipids and encapsulated model drugs from cationic liposomes with different uptake pathways
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/5bb311f7e17e4e038151561b63b90d81
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Intracellular Distribution of Lipids and Encapsulated Model Drugs from Cationic Liposomes with Different Uptake Pathways

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