In vivo liquid biopsy for glioblastoma malignancy by the AFM and LSPR based sensing of exosomal CD44 and CD133 in a mouse model

Abhimanyu Thakur; Chen Xu; Wing Kar Li; Guangyu Qiu; Bing He; Siu-Pang Ng; Chi-Man Lawrence Wu; Youngjin Lee

doi:10.1016/j.bios.2021.113476

In vivo liquid biopsy for glioblastoma malignancy by the AFM and LSPR based sensing of exosomal CD44 and CD133 in a mouse model

Biosens Bioelectron. 2021 Nov 1:191:113476. doi: 10.1016/j.bios.2021.113476. Epub 2021 Jul 2.

Authors

Abhimanyu Thakur¹, Chen Xu², Wing Kar Li³, Guangyu Qiu⁴, Bing He¹, Siu-Pang Ng⁵, Chi-Man Lawrence Wu⁶, Youngjin Lee⁷

Affiliations

¹ Department of Neuroscience, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, SAR, China.
² Department of Materials Science and Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, SAR, China.
³ Department of Biomedical Sciences, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, SAR, China.
⁴ Department of Materials Science and Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, SAR, China; Department of Civil, Environmental and Geomatic Engineering, Institute of Environmental Engineering, ETH Zürich, Zürich, 8093, Switzerland.
⁵ Rafael Biotechnology Company Ltd., SAR, China.
⁶ Department of Materials Science and Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, SAR, China. Electronic address: lawrence.wu@cityu.edu.hk.
⁷ Department of Neuroscience, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, SAR, China. Electronic address: younglee@cityu.edu.hk.

PMID: 34246124
DOI: 10.1016/j.bios.2021.113476

Abstract

Glioblastoma (GBM) is the fatal brain tumor in which secreted lactate enhances the expression of cluster of differentiation 44 (CD44) and the release of exosomes, cell-derived nanovesicles (30-200 nm), and therefore promotes tumor malignant progression. This study found that lactate-driven upregulated CD44 in malignant Glioblastoma cells (GMs) enhanced the release of CD44-enriched exosomes which increased GMs' migration and endothelial cells' tube formation, and CD44 in the secreted exosomes was sensitively detected by "capture and sensing" Titanium Nitride (TiN) - Nanoholes (NH) - discs immunocapture (TIC) - atomic force microscopy (AFM) and ultrasensitive TiN-NH-localized surface plasmon resonance (LSPR) biosensors. The limit of detection for exosomal CD44 with TIC-AFM- and TiN-NH-LSPR-biosensors was 5.29 × 10^-1 μg/ml and 3.46 × 10^-3 μg/ml in exosome concentration, respectively. Importantly, this work first found that label-free sensitive TiN-NH-LSPR biosensor could detect and quantify enhanced CD44 and CD133 levels in immunocaptured GMs-derived exosomes in the blood and the cerebrospinal fluid of a mouse model of GBM, supporting its potential application in a minimally invasive molecular diagnostic for GBM progression as liquid biopsy.

Keywords: AFM; CD44 and CD133; Exosomes; Glioblastoma; LSPR; Lactate.

MeSH terms

Animals
Biosensing Techniques*
Cell Differentiation
Endothelial Cells
Exosomes*
Glioblastoma*
Liquid Biopsy
Mice
Microscopy, Atomic Force
Surface Plasmon Resonance