Simple and Rapid Tumor EV Enrichment Enabled by Long DNA Probe-Guided Entanglement
Dr. Yuanjie Liu
Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 China
Department of Clinical Laboratory, Qianjiang Key Laboratory of Chongqing Qianjiang Central Hospital Laboratory Medicine, Chongqing University Qianjiang Hospital (Qianjiang Central Hospital of Chongqing), Chongqing, 409000 China
These authors contributed equally to this work.
Search for more papers by this authorDr. Yunpeng Fan
Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 China
Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, Department of Laboratory Medicine, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400016 China
These authors contributed equally to this work.
Search for more papers by this authorProf. Xiaoqiang Li
Department of Clinical Laboratory, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Key Laboratory of Child Health and Nutrition, Children's Hospital of Chongqing Medical University, Chongqing, 400016 China
These authors contributed equally to this work.
Search for more papers by this authorProf. Gang Tian
Department of Laboratory Medicine, Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, The Affiliated Hospital of Southwest Medical University, Sichuan, 646000 China
Search for more papers by this authorProf. Bo Shen
Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, Department of Laboratory Medicine, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400016 China
Search for more papers by this authorDr. Menghan Li
Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 China
Search for more papers by this authorDr. Kai Su
Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 China
Search for more papers by this authorDr. Xuhuai Fu
Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 China
Search for more papers by this authorDr. Mengxuan Zhang
Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 China
Search for more papers by this authorCorresponding Author
Prof. Yonghong Wang
Department of Clinical Laboratory, Qianjiang Key Laboratory of Chongqing Qianjiang Central Hospital Laboratory Medicine, Chongqing University Qianjiang Hospital (Qianjiang Central Hospital of Chongqing), Chongqing, 409000 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Prof. Xinyu Li
Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 China
Department of Laboratory Medicine, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, Core Unit of National Clinical Research Center for Laboratory Medicine, University of Science and Technology of China, Hefei, Anhui, 230001 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Prof. Xinmin Li
Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, Department of Laboratory Medicine, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400016 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Prof. Shijia Ding
Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]
Search for more papers by this authorDr. Yuanjie Liu
Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 China
Department of Clinical Laboratory, Qianjiang Key Laboratory of Chongqing Qianjiang Central Hospital Laboratory Medicine, Chongqing University Qianjiang Hospital (Qianjiang Central Hospital of Chongqing), Chongqing, 409000 China
These authors contributed equally to this work.
Search for more papers by this authorDr. Yunpeng Fan
Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 China
Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, Department of Laboratory Medicine, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400016 China
These authors contributed equally to this work.
Search for more papers by this authorProf. Xiaoqiang Li
Department of Clinical Laboratory, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing Key Laboratory of Child Health and Nutrition, Children's Hospital of Chongqing Medical University, Chongqing, 400016 China
These authors contributed equally to this work.
Search for more papers by this authorProf. Gang Tian
Department of Laboratory Medicine, Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, The Affiliated Hospital of Southwest Medical University, Sichuan, 646000 China
Search for more papers by this authorProf. Bo Shen
Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, Department of Laboratory Medicine, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400016 China
Search for more papers by this authorDr. Menghan Li
Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 China
Search for more papers by this authorDr. Kai Su
Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 China
Search for more papers by this authorDr. Xuhuai Fu
Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 China
Search for more papers by this authorDr. Mengxuan Zhang
Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 China
Search for more papers by this authorCorresponding Author
Prof. Yonghong Wang
Department of Clinical Laboratory, Qianjiang Key Laboratory of Chongqing Qianjiang Central Hospital Laboratory Medicine, Chongqing University Qianjiang Hospital (Qianjiang Central Hospital of Chongqing), Chongqing, 409000 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Prof. Xinyu Li
Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 China
Department of Laboratory Medicine, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, Core Unit of National Clinical Research Center for Laboratory Medicine, University of Science and Technology of China, Hefei, Anhui, 230001 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Prof. Xinmin Li
Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, Department of Laboratory Medicine, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400016 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Prof. Shijia Ding
Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]
Search for more papers by this authorGraphical Abstract
The selective isolation of extracellular vesicle (EV) subpopulations is essential for their biomedical applications. We present a simple, rapid, and versatile strategy termed LODGE (Long DNA Probe-Guided EV Entanglement) for the enrichment of tumor-derived EVs (tEVs) from biofluids. LODGE facilitates the application of tEVs in biomarker discovery, therapeutic agents, and disease diagnosis, as evidenced by proteomic profiling, bioactivity assays, and cancer classification.
Abstract
Specific subpopulations of extracellular vesicles (EVs) hold significant clinical potential for biomarker discovery, disease diagnosis, and therapeutic agents. However, this field remains underutilized due to the lack of straightforward and versatile techniques for isolating EV subpopulations from biofluids. Here, we present LODGE, a long DNA probe-guided EV entanglement strategy for the simple, rapid, and selective enrichment of tumor-derived EVs (tEVs) from clinical specimens. LODGE uses two long DNA affinity probes to recognize specific subpopulations, causing them to aggregate with the assistance of splint strands, thereby achieving nondestructive, high-yield, and high-purity separation of tEVs within a short period. Proteomic analysis revealed that the isolated tEVs contributed to the identification of tumor-associated biomarkers compared to total EVs. Additionally, by incorporating a split G-quadruplex-containing molecular trap domain, a novel structure that significantly improves the fluorescence emission of thioflavin T (ThT), into DNA affinity probes, we developed an innovative LODGE-ThT sensing strategy for the highly sensitive profiling of multiple tEV subpopulations. Using data from the tEVs alongside clinical indicators processed with machine learning algorithms, we effectively classified five tumor types. Our results show that LODGE is a promising tool for identifying specific EV subpopulations, and fostering their biomedical applications.
Conflict of Interests
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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