Enhanced exosome capture in urine using aptamer-modified temperature-responsive polymer for sensitive early detection of bladder cancer

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作者
Liu, Min [1 ,2 ]
Yi, Kezhen [1 ,2 ]
Zhang, Yaran [3 ]
Long, Fei [1 ,2 ]
Hu, Xin [1 ,2 ]
Jia, Gaihua [1 ,2 ]
Xiao, Ting [1 ,2 ]
Xu, Xianqun [1 ]
Duan, Yongwei [1 ]
Shi, Hongjie [4 ]
Yao, Zhipeng [5 ]
Liu, Tongzu [6 ]
He, Zhike [3 ,7 ]
Liu, Zheng [5 ]
Wang, Fubing [1 ,2 ,8 ]
Wang, Xinghuan [6 ,8 ]
机构
[1] Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan,430071, China
[2] Center for Single-Cell Omics and Tumor Liquid Biopsy, Zhongnan Hospital of Wuhan University, Wuhan,430071, China
[3] College of Chemistry and Molecular Sciences, Wuhan University, Wuhan,430072, China
[4] Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan,430071, China
[5] Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan,430030, China
[6] Department of Urology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan,430071, China
[7] Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Province Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan,430071, China
[8] Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan,430071, China
关键词
Current methods for bladder cancer (BCa) detection are often invasive and yield unsatisfactory diagnostic performance; especially for low-grade and early-stage tumors. Exosome biomarkers in urine offer excellent potential for improving the non-invasive early diagnosis of BCa. However; the lack of an efficient exosome isolation strategy poses a challenge for clinical application. This study presents a strategy for homogeneous exosome capture to enhance enrichment efficiency. We decorated exosome-specific aptamers onto a temperature-responsive polymer. Subsequently; leveraging the thermoresponsive properties of the polymer; which can transition between homogeneous and heterogeneous states at different temperatures; we achieved efficient homogeneous capture and rapid heterogeneous separation of urinary exosomes. The procedure; conducted at a relatively low temperature; enables rapid exosome isolation (within 5 min) without ultracentrifugation; facilitating clinical application. The developed exosome enrichment method using the functionalized temperature-responsive polymer offers significant advantages: an efficient; rapid; low-cost method that is widely applicable. Exosomes from urine samples; enriched using a functionalized temperature-responsive polymer; established a diagnostic model; exhibiting significant improved sensitivity over fluorescence in situ hybridization (FISH); particularly for early-stage (88.7% vs. 49.1%) and low-grade BCa (82.6% vs. 26.1%). This non-invasive; reliable BCa detection method holds promising potential for clinical use. © 2024 Elsevier B.V;
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