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
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.