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Nano Research

Article Title

Fluorescent glycan nanoparticle-based FACS assays for the identification of genuine drug-resistant cancer cells with differentiation potential

Authors

Chenglong Wang, The State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China Research Center for Clinical Research, Jinshan Hospital, Fudan University, Shanghai 200540, China
Wencai Guan, Research Center for Clinical Research, Jinshan Hospital, Fudan University, Shanghai 200540, China
Rong Chen, Department of Respiratory and Critical Care Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China Institute of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China
Yael Levi-Kalisman, The Center for Nanoscience and Nanotechnology and the Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91905, Israel
Yichun Xu, Shanghai Biochip Co. Ltd. and National Engineering Center for Biochip at Shanghai, Shanghai 201203, China
Liwen Zhang, Shanghai Biochip Co. Ltd. and National Engineering Center for Biochip at Shanghai, Shanghai 201203, China
Min Zhou, Department of Respiratory and Critical Care Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China Institute of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China
Guoxiong Xu, Research Center for Clinical Research, Jinshan Hospital, Fudan University, Shanghai 200540, China
Hongjing Dou, The State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China

Keywords

glycan nanoparticle, FACS assays, drug resistance, tumor heterogeneity, diagnose

Abstract

Herein we develop a unique differentiated-uptake strategy capable of efficient and high-purity isolation of genuine drug-resistant (DR) cells from three types of drug-surviving cancer cells, which include paclitaxel-surviving human ovarian OVCAR-3 cancer cells and human lung carcinoma A549/Taxol cells, and doxorubicin-surviving human immortalized myelogenous leukemia K562/ADR cells. By using this strategy which relies on fluorescent glycan nanoparticle (FGNP)-based fluorescence-activated cell sorting (FACS) assays, two subpopulations with distinct fluorescences existing in drug-surviving OVCAR-3 cells were separated, and we found that the lower fluorescence (LF) subpopulation consisted of DR cells, while the higher fluorescence (HF) subpopulation was comprised of non-DR cells. Besides, the DR cells and their progenies were found distinct in their increased expression of drug-resistant genes. More intriguingly, by using the FGNP-based FACS assay to detect DR/non-DR phenotypes, we found that the DR phenotype had a potential to differentiate into the non-DR progeny, which demonstrates the differentiation feature of stem-like cancer cells. Further research disclosed that the assay can quantitatively detect the degree of drug resistance in DR cells, as well as the reversal of drug resistance that are tackled by various therapeutic methods. The strategy thus paves the way to develop theranostic approaches associated with chemotherapy-resistance and cancer stemness.

Graphical Abstract

Publisher

Tsinghua University Press

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