Engineering Tumour Cell-Binding Synthetic Polymers with Sensing Dense Transporters Associated with Aberrant Glutamine Metabolism

Abstract Increased glutamine uptake toward the elevated glutaminolysis is one of the hallmarks of tumour cells. This aberrant glutamine metabolism has recently attracted considerable attention as a diagnostic and therapeutic target. Herein, we developed glutamine-functionalized polymer to achieve a...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Naoki Yamada, Yuto Honda, Hiroyasu Takemoto, Takahiro Nomoto, Makoto Matsui, Keishiro Tomoda, Masamitsu Konno, Hideshi Ishii, Masaki Mori, Nobuhiro Nishiyama
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/665b0b3bab784948b6418dbdebcd15fb
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:665b0b3bab784948b6418dbdebcd15fb
record_format	dspace
spelling	oai:doaj.org-article:665b0b3bab784948b6418dbdebcd15fb2021-12-02T12:32:26ZEngineering Tumour Cell-Binding Synthetic Polymers with Sensing Dense Transporters Associated with Aberrant Glutamine Metabolism10.1038/s41598-017-06438-y2045-2322https://doaj.org/article/665b0b3bab784948b6418dbdebcd15fb2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06438-yhttps://doaj.org/toc/2045-2322Abstract Increased glutamine uptake toward the elevated glutaminolysis is one of the hallmarks of tumour cells. This aberrant glutamine metabolism has recently attracted considerable attention as a diagnostic and therapeutic target. Herein, we developed glutamine-functionalized polymer to achieve a selective high affinity to tumour cells overexpressing glutaminolysis-related transporter ASCT2. In in vitro study, our developed polymer exhibited faster and higher cellular uptake in tumour cells than that in normal cells. Uptake inhibition study revealed the dominant contribution of ASCT2 to the polymer-cell interaction. Furthermore, the binding affinity of the polymer to tumour cells was estimated to be comparable to that of the potent ligand molecules reported in the literature. In in vivo study, the polymer showed prolonged retention at tumour site after intratumoral injection. This study offers a novel approach for designing tumour cell-binding synthetic polymers through the recognition of dense transporters related to tumour-associated metabolism.Naoki YamadaYuto HondaHiroyasu TakemotoTakahiro NomotoMakoto MatsuiKeishiro TomodaMasamitsu KonnoHideshi IshiiMasaki MoriNobuhiro NishiyamaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Naoki Yamada Yuto Honda Hiroyasu Takemoto Takahiro Nomoto Makoto Matsui Keishiro Tomoda Masamitsu Konno Hideshi Ishii Masaki Mori Nobuhiro Nishiyama Engineering Tumour Cell-Binding Synthetic Polymers with Sensing Dense Transporters Associated with Aberrant Glutamine Metabolism
description	Abstract Increased glutamine uptake toward the elevated glutaminolysis is one of the hallmarks of tumour cells. This aberrant glutamine metabolism has recently attracted considerable attention as a diagnostic and therapeutic target. Herein, we developed glutamine-functionalized polymer to achieve a selective high affinity to tumour cells overexpressing glutaminolysis-related transporter ASCT2. In in vitro study, our developed polymer exhibited faster and higher cellular uptake in tumour cells than that in normal cells. Uptake inhibition study revealed the dominant contribution of ASCT2 to the polymer-cell interaction. Furthermore, the binding affinity of the polymer to tumour cells was estimated to be comparable to that of the potent ligand molecules reported in the literature. In in vivo study, the polymer showed prolonged retention at tumour site after intratumoral injection. This study offers a novel approach for designing tumour cell-binding synthetic polymers through the recognition of dense transporters related to tumour-associated metabolism.
format	article
author	Naoki Yamada Yuto Honda Hiroyasu Takemoto Takahiro Nomoto Makoto Matsui Keishiro Tomoda Masamitsu Konno Hideshi Ishii Masaki Mori Nobuhiro Nishiyama
author_facet	Naoki Yamada Yuto Honda Hiroyasu Takemoto Takahiro Nomoto Makoto Matsui Keishiro Tomoda Masamitsu Konno Hideshi Ishii Masaki Mori Nobuhiro Nishiyama
author_sort	Naoki Yamada
title	Engineering Tumour Cell-Binding Synthetic Polymers with Sensing Dense Transporters Associated with Aberrant Glutamine Metabolism
title_short	Engineering Tumour Cell-Binding Synthetic Polymers with Sensing Dense Transporters Associated with Aberrant Glutamine Metabolism
title_full	Engineering Tumour Cell-Binding Synthetic Polymers with Sensing Dense Transporters Associated with Aberrant Glutamine Metabolism
title_fullStr	Engineering Tumour Cell-Binding Synthetic Polymers with Sensing Dense Transporters Associated with Aberrant Glutamine Metabolism
title_full_unstemmed	Engineering Tumour Cell-Binding Synthetic Polymers with Sensing Dense Transporters Associated with Aberrant Glutamine Metabolism
title_sort	engineering tumour cell-binding synthetic polymers with sensing dense transporters associated with aberrant glutamine metabolism
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/665b0b3bab784948b6418dbdebcd15fb
work_keys_str_mv	AT naokiyamada engineeringtumourcellbindingsyntheticpolymerswithsensingdensetransportersassociatedwithaberrantglutaminemetabolism AT yutohonda engineeringtumourcellbindingsyntheticpolymerswithsensingdensetransportersassociatedwithaberrantglutaminemetabolism AT hiroyasutakemoto engineeringtumourcellbindingsyntheticpolymerswithsensingdensetransportersassociatedwithaberrantglutaminemetabolism AT takahironomoto engineeringtumourcellbindingsyntheticpolymerswithsensingdensetransportersassociatedwithaberrantglutaminemetabolism AT makotomatsui engineeringtumourcellbindingsyntheticpolymerswithsensingdensetransportersassociatedwithaberrantglutaminemetabolism AT keishirotomoda engineeringtumourcellbindingsyntheticpolymerswithsensingdensetransportersassociatedwithaberrantglutaminemetabolism AT masamitsukonno engineeringtumourcellbindingsyntheticpolymerswithsensingdensetransportersassociatedwithaberrantglutaminemetabolism AT hideshiishii engineeringtumourcellbindingsyntheticpolymerswithsensingdensetransportersassociatedwithaberrantglutaminemetabolism AT masakimori engineeringtumourcellbindingsyntheticpolymerswithsensingdensetransportersassociatedwithaberrantglutaminemetabolism AT nobuhironishiyama engineeringtumourcellbindingsyntheticpolymerswithsensingdensetransportersassociatedwithaberrantglutaminemetabolism
_version_	1718394098038079488

Engineering Tumour Cell-Binding Synthetic Polymers with Sensing Dense Transporters Associated with Aberrant Glutamine Metabolism

Ejemplares similares