Department of Neuroscience, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, SAR, China.
Department of Materials Science and Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, SAR, China.
Biosens Bioelectron. 2021 Nov 1;191:113476. doi: 10.1016/j.bios.2021.113476. Epub 2021 Jul 2.
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 μg/ml and 3.46 × 10 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.
胶质母细胞瘤（GBM）是致命的脑肿瘤，其中分泌的乳酸增强了分化群 44（CD44）的表达和外泌体的释放，细胞衍生的纳米囊泡（30-200nm），从而促进肿瘤恶性进展。本研究发现，乳酸驱动的恶性胶质母细胞瘤细胞（GMs）中上调的 CD44 增强了富含 CD44 的外泌体的释放，增加了 GMs 的迁移和内皮细胞的管形成，并且分泌的外泌体中的 CD44 可以通过“捕获和传感”氮化钛（TiN）-纳米孔（NH）-盘免疫捕获（TIC）-原子力显微镜（AFM）和超灵敏 TiN-NH-局部表面等离子体共振（LSPR）生物传感器灵敏地检测到。TIC-AFM-和 TiN-NH-LSPR 生物传感器检测外泌体 CD44 的检测限分别为外泌体浓度的 5.29×10μg/ml 和 3.46×10μg/ml。重要的是，这项工作首次发现，无标记敏感的 TiN-NH-LSPR 生物传感器可以检测和定量免疫捕获的 GMs 衍生的外泌体中增强的 CD44 和 CD133 水平，在 GBM 小鼠模型的血液和脑脊液中，支持其在作为液体活检的 GBM 进展的微创分子诊断中的潜在应用。
