Boronic Acid Ligands Can Target Multiple Subpopulations of Pancreatic Cancer Stem Cells via pH-Dependent Glycan-Terminal Sialic Acid Recognition

Takuya Miyazaki; Thahomina Khan; Yoshihiro Tachihara; Michiko Itoh; Taiki Miyazawa; Takayoshi Suganami; Yuji Miyahara; Horacio Cabral; Akira Matsumoto

doi:10.1021/acsabm.1c00383

Boronic Acid Ligands Can Target Multiple Subpopulations of Pancreatic Cancer Stem Cells via pH-Dependent Glycan-Terminal Sialic Acid Recognition

Takuya Miyazaki, Thahomina Khan, Yoshihiro Tachihara, Michiko Itoh, Taiki Miyazawa, Takayoshi Suganami, Yuji Miyahara, Horacio Cabral, Akira Matsumoto

New Industry Creation Hatchery Center (NICHe)

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

Eradication of cancer stem cells (CSCs) is an ultimate goal in cancer chemotherapy. Although a ligand-assisted targeting approach seems rational, the existence of subpopulations of CSCs and their discrimination from those present on healthy sites makes it a severe challenge. Some boronic acid (BA) derivatives are known for the ability to bind with glycan-terminal sialic acid (SA), in a manner dependent on the acidification found in hypoxic tumoral microenvironment. Taking advantage of this feature, here we show that the BA-ligand fluorescence conjugate can effectively target multiple CSC subpopulations in parallel, which otherwise must be independently aimed when using antibody - ligands.

Original language	English
Pages (from-to)	6647-6651
Number of pages	5
Journal	ACS Applied Bio Materials
Volume	4
Issue number	9
DOIs	https://doi.org/10.1021/acsabm.1c00383
Publication status	Published - 2021 Sept 20

Keywords

active targeting
boronic acids
cancer stem cells
pancreatic cancer
sialic acids
stimuli-response

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acsabm.1c00383

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abstract = "Eradication of cancer stem cells (CSCs) is an ultimate goal in cancer chemotherapy. Although a ligand-assisted targeting approach seems rational, the existence of subpopulations of CSCs and their discrimination from those present on healthy sites makes it a severe challenge. Some boronic acid (BA) derivatives are known for the ability to bind with glycan-terminal sialic acid (SA), in a manner dependent on the acidification found in hypoxic tumoral microenvironment. Taking advantage of this feature, here we show that the BA-ligand fluorescence conjugate can effectively target multiple CSC subpopulations in parallel, which otherwise must be independently aimed when using antibody - ligands.",

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note = "Funding Information: This work was supported in part by the funding from Kanagawa Institute of Industrial Science and Technology (KISTEC), Program for Building Regional Innovation Ecosystems from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT), Grants-in Aid from Research Activity Start-up (JP19K23614; T.M.) from the Japan Society for the Promotion of Science (JSPS), Grants-in-Aid from The Uehara Memorial Foundation (201910255; T.M.), Grants-in-Aid from Fukuda Foundation for Medical Technology (T.M.), GSK Japan Research Grant 2020 from GlaxoSmithKline plc (T.M.). Publisher Copyright: {\textcopyright}",

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AU - Miyazaki, Takuya

AU - Khan, Thahomina

AU - Tachihara, Yoshihiro

AU - Itoh, Michiko

AU - Miyazawa, Taiki

AU - Suganami, Takayoshi

AU - Miyahara, Yuji

AU - Cabral, Horacio

AU - Matsumoto, Akira

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PY - 2021/9/20

Y1 - 2021/9/20

N2 - Eradication of cancer stem cells (CSCs) is an ultimate goal in cancer chemotherapy. Although a ligand-assisted targeting approach seems rational, the existence of subpopulations of CSCs and their discrimination from those present on healthy sites makes it a severe challenge. Some boronic acid (BA) derivatives are known for the ability to bind with glycan-terminal sialic acid (SA), in a manner dependent on the acidification found in hypoxic tumoral microenvironment. Taking advantage of this feature, here we show that the BA-ligand fluorescence conjugate can effectively target multiple CSC subpopulations in parallel, which otherwise must be independently aimed when using antibody - ligands.

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Boronic Acid Ligands Can Target Multiple Subpopulations of Pancreatic Cancer Stem Cells via pH-Dependent Glycan-Terminal Sialic Acid Recognition

Abstract

Keywords

UN SDGs

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