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Yu Y, Zhang W, Ding Q, Cheng X, Wang K, Zhang G, Jiang B, Yu X, Li YT, Zhang GJ. Dual-antibody functionalized transistor biosensor for specific diagnosis of liver cancer. Talanta 2025; 293:128095. [PMID: 40203597 DOI: 10.1016/j.talanta.2025.128095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2025] [Revised: 03/29/2025] [Accepted: 04/05/2025] [Indexed: 04/11/2025]
Abstract
Selectively and sensitively detecting specific exosomal markers is critical for early diagnosis of liver cancer. However, identifying specific exosomal biomarkers and establishing accurate, convenient detection methods remain challenging. In this study, we used bioinformatics to identify the higher levels of EpCAM and GPC-3 proteins on liver cancer exosomes. These markers were used to create a dual-antibody functionalized transistor biosensor for precise detection of liver cancer exosomes. The techniques exhibited outstanding specificity and sensitivity. Detection thresholds in PBS and simulated plasma were established at 20 particles/μL and 47 particles/μL, respectively, facilitating the distinction of liver cancer cell-derived exosomes from those originating from various other cancer cells. Furthermore, in clinical samples testing, this approach not only distinguished clinical samples among liver cancer patients and healthy individuals, but also demonstrated the ability to differentiate liver cancer from other types of tumors, achieving a precision and accuracy rate of 100 %. The developed biosensor demonstrates excellent potential for clinical application and this work offers a promising and effective approach for cancer diagnosis.
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Affiliation(s)
- Yi Yu
- School of Laboratory Medicine, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan, 430065, PR China; Hubei Shizhen Laboratory, Wuhan, 430065, Hubei, PR China
| | - Wenhao Zhang
- School of Laboratory Medicine, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan, 430065, PR China
| | - Qiyue Ding
- School of Laboratory Medicine, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan, 430065, PR China
| | - Xiaolu Cheng
- School of Laboratory Medicine, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan, 430065, PR China
| | - Kaiwei Wang
- School of Laboratory Medicine, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan, 430065, PR China
| | - Guangxin Zhang
- School of Laboratory Medicine, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan, 430065, PR China
| | - Boan Jiang
- School of Laboratory Medicine, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan, 430065, PR China
| | - Xionghua Yu
- Xiantao Hospital of Traditional Chinese Medicine, Xiantao, Hubei, 433000, PR China.
| | - Yu-Tao Li
- School of Laboratory Medicine, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan, 430065, PR China; Hubei Shizhen Laboratory, Wuhan, 430065, Hubei, PR China.
| | - Guo-Jun Zhang
- School of Laboratory Medicine, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan, 430065, PR China; Hubei Shizhen Laboratory, Wuhan, 430065, Hubei, PR China.
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2
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Sonar S, Das A, Yeong Zher L, Narayanan Ravi R, Zheng Kong EQ, Dhar R, Narayanan K, Gorai S, Subramaniyan V. Exosome-Based Sensor: A Landmark of the Precision Cancer Diagnostic Era. ACS APPLIED BIO MATERIALS 2025. [PMID: 40366154 DOI: 10.1021/acsabm.5c00288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/15/2025]
Abstract
Extracellular vesicles are nanoscale vesicles released by a diversity of cells that mediate intercellular communication by transporting an array of biomolecules. They are gaining increasing attention in cancer research due to their ability to carry specific biomarkers. This characteristic makes them potentially useful for highly sensitive, noninvasive diagnostic procedures and more precise prognostic assessments. Consequently, EVs are emerging as a transformative tool in cancer treatment, facilitating early detection and personalized medicine. Despite significant progress, clinical implementation is hindered by challenges in EV isolation, purification, and characterization. However, developing advanced biosensor technologies offers promising solutions to these obstacles. This review highlights recent progress in biosensors for EV detection and analysis, focusing on various sensing modalities including optical, electrochemical, microfluidic, nanomechanical, and biological sensors. We also explore techniques for EV isolation, characterization, and analysis, such as electron microscopy, atomic force microscopy, nanoparticle tracking analysis, and single-particle analysis. Furthermore, the review critically assesses the challenges associated with EV detection and put forward future directions, aiming to usher in a cutting-edge era of precision medicine through advanced, sensor-based, noninvasive early cancer diagnosis by detecting EV-carried biomarkers.
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Affiliation(s)
- Swarup Sonar
- Department of Oncology, Neuron Institute of Applied Research, Amravati, Maharashtra 444605, India
| | - Asmit Das
- Department of Oncology, Neuron Institute of Applied Research, Amravati, Maharashtra 444605, India
| | - Lee Yeong Zher
- Monash University Malaysia, Bandar Sunway, Subang Jaya 47500, Selangor, Malaysia
| | - Ram Narayanan Ravi
- Monash University Malaysia, Bandar Sunway, Subang Jaya 47500, Selangor, Malaysia
| | - Eason Qi Zheng Kong
- Monash University Malaysia, Bandar Sunway, Subang Jaya 47500, Selangor, Malaysia
| | - Rajib Dhar
- Division of Pharmacology, Faculty of Medical and Life Sciences, Sunway University, Bandar Sunway, Subang Jaya 47500, Selangor (Darul Ehsan), Malaysia
| | - Kumaran Narayanan
- Monash University Malaysia, Bandar Sunway, Subang Jaya 47500, Selangor, Malaysia
| | - Sukhamoy Gorai
- Department of Neurological Sciences, Rush University Medical Center, 1620 W Harrison Street, Chicago, Illinois 60612, United States
| | - Vetriselvan Subramaniyan
- Division of Pharmacology, Faculty of Medical and Life Sciences, Sunway University, Bandar Sunway, Subang Jaya 47500, Selangor (Darul Ehsan), Malaysia
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Zhang Y, Yue NN, Chen LY, Tian CM, Yao J, Wang LS, Liang YJ, Wei DR, Ma HL, Li DF. Exosomal biomarkers: A novel frontier in the diagnosis of gastrointestinal cancers. World J Gastrointest Oncol 2025; 17:103591. [PMID: 40235899 PMCID: PMC11995328 DOI: 10.4251/wjgo.v17.i4.103591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 01/24/2025] [Accepted: 02/25/2025] [Indexed: 03/25/2025] Open
Abstract
Gastrointestinal (GI) cancers, which predominantly manifest in the stomach, colorectum, liver, esophagus, and pancreas, accounting for approximately 35% of global cancer-related mortality. The advent of liquid biopsy has introduced a pivotal diagnostic modality for the early identification of premalignant GI lesions and incipient cancers. This non-invasive technique not only facilitates prompt therapeutic intervention, but also serves as a critical adjunct in prognosticating the likelihood of tumor recurrence. The wealth of circulating exosomes present in body fluids is often enriched with proteins, lipids, microRNAs, and other RNAs derived from tumor cells. These specific cargo components are reflective of processes involved in GI tumorigenesis, tumor progression, and response to treatment. As such, they represent a group of promising biomarkers for aiding in the diagnosis of GI cancer. In this review, we delivered an exhaustive overview of the composition of exosomes and the pathways for cargo sorting within these vesicles. We laid out some of the clinical evidence that supported the utilization of exosomes as diagnostic biomarkers for GI cancers and discussed their potential for clinical application. Furthermore, we addressed the challenges encountered when harnessing exosomes as diagnostic and predictive instruments in the realm of GI cancers.
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Affiliation(s)
- Yuan Zhang
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
- Department of Medical Administration, Huizhou Institute for Occupational Health, Huizhou 516000, Guangdong Province, China
| | - Ning-Ning Yue
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University), Shenzhen 518000, Guangdong Province, China
| | - Li-Yu Chen
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
| | - Cheng-Mei Tian
- Department of Emergency, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
| | - Jun Yao
- Department of Gastroenterology, Shenzhen People’s Hospital (Jinan University of Second Clinical Medical Sciences), Shenzhen 518000, Guangdong Province, China
| | - Li-Sheng Wang
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
| | - Yu-Jie Liang
- Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital, Shenzhen 518000, Guangdong Province, China
| | - Dao-Ru Wei
- Department of Rehabilitation, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
| | - Hua-Lin Ma
- Department of Nephrology, The Second Clinical Medical College, Jinan University, Shenzhen 518020, Guangdong Province, China
| | - De-Feng Li
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, Guangdong Province, China
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Shi X, Zhang T, Zhu S, Ning L, Cheng H, Yu F, Tian S. A catalytic assembly triggered DNAzyme motor on spherical nucleic acids for sensitive small extracellular vesicle detection. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2024; 17:77-83. [PMID: 39565170 DOI: 10.1039/d4ay01845a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2024]
Abstract
The expression levels of small extracellular vesicles (sEVs) are closely associated with several significant biological processes, which can be used as a crucial biomarker for cancer diagnosis, such as colorectal cancer. More efforts are still necessary to amplify sEV detection sensitivity, as their expression is minimal during the early stages of colorectal cancer. Through the integration of a catalytic assembly-triggered DNAzyme motor and gold nanoparticle (AuNP) aggregation, we have developed a triple signal amplified biosensor for the detection of sEVs. In this method, the catalytic assembly triggered DNAzyme motor continuously cleaved on the hairpin probe which is fixed on the surface of AuNPs, leaving a single-stranded sequence on the surface of AuNPs to induce the aggregation. This approach employs a triple signal amplification process to enhance the efficiency of the reaction and circumvent the issue of expensive and readily degradable proteases. The signal output system is based on dynamic light scattering technology, which enables ultra-sensitive detection of sEVs with a detection limit of 3.08 particles per μL. The present strategy exhibits significant potential for the analysis of a variety of additional analytes in clinical research disciplines due to its appealing analytical capabilities.
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Affiliation(s)
- Xiaoying Shi
- Department of Gastroenterology, Chenjiaqiao Hospital of Shapingba District Affiliated to Chongqing Medical and Pharmaceutical College, Chongqing, 401331, China.
| | - Tingting Zhang
- Department of Gastroenterology, Chenjiaqiao Hospital of Shapingba District Affiliated to Chongqing Medical and Pharmaceutical College, Chongqing, 401331, China.
| | - Shisheng Zhu
- College of Chongqing Medical and Pharmaceutical College, Chongqing, 401331, China
| | - Linhong Ning
- College of Chongqing Medical and Pharmaceutical College, Chongqing, 401331, China
| | - Heng Cheng
- Department of Gastroenterology, Chenjiaqiao Hospital of Shapingba District Affiliated to Chongqing Medical and Pharmaceutical College, Chongqing, 401331, China.
| | - Feng Yu
- Department of Gastroenterology, Chenjiaqiao Hospital of Shapingba District Affiliated to Chongqing Medical and Pharmaceutical College, Chongqing, 401331, China.
| | - Shanshan Tian
- Pre-hospital Emergency Department, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, 400014, China.
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5
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He Y, Ren Y, Tang J. Immobilization coupling with aptamer assisted dual cycle amplification for sensitive sEVs isolation and analysis. Biotechnol Lett 2024; 46:1049-1056. [PMID: 39266887 DOI: 10.1007/s10529-024-03526-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 08/07/2024] [Accepted: 08/12/2024] [Indexed: 09/14/2024]
Abstract
Precise identification of small extracellular vesicles (sEVs) is crucial for improving disease diagnosis and treatments, such as bladder cancer. However, accurate isolation and simultaneously quantification of sEVs remain a huge challenge. We have introduced a new technique that combines immobilization with aptamer-assisted dual cycle amplification to isolate and analyze sEVs with high sensitivity. In this method, the CD9 protein antibody is attached to the plate's surface for the initial identification of sEVs, while an aptamer probe is used to detect the exosomal surface protein CD63. We have created an sEVs-surface method that combines target recognition initiated signal recycling and rolling circle amplification (RCA) for signal amplification. This approach allows for the "AND" logic analysis of dual biomarkers, enabling both sEVs quantification and tracing. The proposed approach has a broad detection range and a low limit of detection. Moreover, the established method showed good stability in detecting sEVs with a low coefficient of variation. Our method can effectively isolate certain sEVs and accurately identify them, making it suitable for many uses in biological science, biomedical engineering, and personalized medicine.
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Affiliation(s)
- Yu He
- Department of Pathology, The Affiliated People's Hospital of Ningbo University, No. 251 Baizhang Road, Yinzhou District, Ningbo, 315040, Zhejiang Province, China.
| | - Ying Ren
- Department of Pathology, The Affiliated People's Hospital of Ningbo University, No. 251 Baizhang Road, Yinzhou District, Ningbo, 315040, Zhejiang Province, China
| | - Jiawen Tang
- Department of Pathology, The Affiliated People's Hospital of Ningbo University, No. 251 Baizhang Road, Yinzhou District, Ningbo, 315040, Zhejiang Province, China
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6
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Zhang G, Cen S, Huang X, Yu X, Zhu H, Sun L, Su R, Yang C, Zhu Z. Size Matters: Curvature and Antigen-Mediated Dual Recognition of Size-Specific Tumor-Derived Exosomes. Anal Chem 2024; 96:17897-17906. [PMID: 39454136 DOI: 10.1021/acs.analchem.4c04769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2024]
Abstract
Accurate identification of tumor-derived exosomes is crucial for advancing cancer diagnosis and therapies. However, distinguishing tumor-derived exosomes is challenging due to the heterogeneity of exosomes, which reflect different sizes and cells of origin. To address this challenge, we introduce the curvature and antigen-mediated proximity ligation assay for tumor-derived exosomes (CAPTURE) strategy, which leverages the size-selective properties of curvature-sensing peptides and specific antigen binding of aptamers. CAPTURE enables highly specific identification and precise quantification of the PD-L1+ exosomes in plasma samples. CAPTURE is proven to be simple, homogeneous, rapid, and highly selective, achieving a 100% specificity in discriminating colorectal cancer (CRC) patients from healthy donors. Overall, the CAPTURE strategy presents a promising avenue for precise and noninvasive cancer diagnosis.
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Affiliation(s)
- Guihua Zhang
- The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China
| | - Shiyun Cen
- The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China
| | - Xiaodan Huang
- The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China
| | - Xiyuan Yu
- The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China
| | - Huanghuang Zhu
- The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China
| | - Leyu Sun
- The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China
| | - Rui Su
- Department of Hematology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361005, China
| | - Chaoyong Yang
- The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China
- Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
| | - Zhi Zhu
- The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China
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7
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Baruah H, Sarma A, Basak D, Das M. Exosome: From biology to drug delivery. Drug Deliv Transl Res 2024; 14:1480-1516. [PMID: 38252268 DOI: 10.1007/s13346-024-01515-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/27/2023] [Indexed: 01/23/2024]
Abstract
In recent years, different advancements have been observed in nanosized drug delivery systems. Factors such as stability, safety and targeting efficiency cause hindrances in the clinical translation of these synthetic nanocarriers. Therefore, researchers employed endogenous nanocarriers like exosomes as drug delivery vehicles that have an inherent ability to target more efficiently after appropriate functionalization and show higher biocompatibility and less immunogenicity and facilitate penetration through the biological barriers more quickly than the other available carriers. Exosomes are biologically derived lipid bilayer-enclosed nanosized extracellular vesicles (size ranges from 30 to 150 nm) secreted from both prokaryotic and eukaryotic cells and appears significantly in the extracellular space. These EVs (extracellular vesicles) can exist in different sources, including mammals, plants and microorganisms. Different advanced techniques have been introduced for the isolation of exosomes to overcome the existing barriers present with conventional methods. Extensive research on the application of exosomes in therapeutic delivery for treating various diseases related to central nervous system, bone, cancer, skin, etc. has been employed. Several studies are on different stages of clinical trials, and many exosomes patents have been registered.
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Affiliation(s)
- Himakshi Baruah
- Advanced Drug Delivery Laboratory, Department of Pharmaceutics, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Guwahati, 781017, Assam, India
| | - Anupam Sarma
- Advanced Drug Delivery Laboratory, Department of Pharmaceutics, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Guwahati, 781017, Assam, India.
| | - Debojeet Basak
- Advanced Drug Delivery Laboratory, Department of Pharmaceutics, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Guwahati, 781017, Assam, India
| | - Mridusmita Das
- Advanced Drug Delivery Laboratory, Department of Pharmaceutics, School of Pharmaceutical Sciences, Girijananda Chowdhury University, Guwahati, 781017, Assam, India
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Shen J, Ma Z, Xu J, Xue T, Lv X, Zhu G, Huang B. Exosome Isolation and Detection: From Microfluidic Chips to Nanoplasmonic Biosensor. ACS APPLIED MATERIALS & INTERFACES 2024. [PMID: 38676635 DOI: 10.1021/acsami.3c19396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/29/2024]
Abstract
Exosomes are becoming more widely acknowledged as significant circulating indicators for the prognosis and diagnosis of cancer. Circulating exosomes are essential to the development and spread of cancer, according to a growing body of research. Using existing technology, characterizing exosomes is quite difficult. Therefore, a direct, sensitive, and targeted approach to exosome detection will aid in illness diagnosis and prognosis. The review discusses the new strategies for exosome isolation and detection technologies from microfluidic chips to nanoplasmonic biosensors, analyzing the advantages and limitations of these new technologies. This review serves researchers to better understand exosome isolation and detection methods and to help develop better exosome isolating and detecting devices for clinical applications.
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Affiliation(s)
- Jianing Shen
- School of Instrument Science and Optoelectronic Engineering, Beijing Information Science and Technology University, Beijing 100192, China
| | - Zhengtai Ma
- Key Laboratory of Optoelectronic Materials and Devices, Chinese Academy of Sciences, Beijing 100083, China
- College of Materials Science and Optoelectronic Technology, University of Chinese, Academy of Sciences, Beijing 100049, China
| | - Jiaqi Xu
- School of Instrument Science and Optoelectronic Engineering, Beijing Information Science and Technology University, Beijing 100192, China
| | - Tianhao Xue
- School of Instrument Science and Optoelectronic Engineering, Beijing Information Science and Technology University, Beijing 100192, China
| | - Xiaoqing Lv
- Key Laboratory of Optoelectronic Materials and Devices, Chinese Academy of Sciences, Beijing 100083, China
| | - Guixian Zhu
- School of Instrument Science and Optoelectronic Engineering, Beijing Information Science and Technology University, Beijing 100192, China
| | - Beiju Huang
- Key Laboratory of Optoelectronic Materials and Devices, Chinese Academy of Sciences, Beijing 100083, China
- College of Materials Science and Optoelectronic Technology, University of Chinese, Academy of Sciences, Beijing 100049, China
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9
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Ramachandran A, Dhar R, Devi A. Stem Cell-Derived Exosomes: An Advanced Horizon to Cancer Regenerative Medicine. ACS APPLIED BIO MATERIALS 2024; 7:2128-2139. [PMID: 38568170 DOI: 10.1021/acsabm.4c00089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/16/2024]
Abstract
Cancer research has made significant progress in recent years, and extracellular vesicles (EVs) based cancer investigation reveals several facts about cancer. Exosomes are a subpopulation of EVs. In the present decade, exosomes is mostly highlighted for cancer theranostic research. Tumor cell derived exosomes (TEXs) promote cancer but there are multiple sources of exosomes that can be used as cancer therapeutic agents (plant exosomes, stem cell-derived exosomes, modified or synthetic exosomes). Stem cells based regenerative medicine faces numerous challenges, such as promote tumor development, cellular reprogramming etc., and therefore addressing these complications becomes essential. Stem cell-derived exosomes serves as an answer to these problems and offers a better solution. Global research indicates that stem cell-derived exosomes also play a dual role in the cellular system by either inhibiting or promoting cancer. Modified exosomes which are genetically engineered exosomes or surface modified exosomes to increase the efficacy of the therapeutic properties can also be considered to target the above concerns. However, the difficulties associated with the exosomes include variations in exosomes heterogenity, isolation protocols, large scale production, etc., and these have to be managed effectively. In this review, we explore exosomes biogenesis, multiple stem cell-derived exosome sources, drug delivery, modified stem cells exosomes, clinical trial of stem cells exosomes, and the related challenges in this domain and future orientation. This article may encourage researchers to explore stem cell-derived exosomes and develop an effective and affordable cancer therapeutic solution.
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Affiliation(s)
- Aparna Ramachandran
- Cancer and Stem Cell Biology Laboratory, Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu 603203, India
| | - Rajib Dhar
- Cancer and Stem Cell Biology Laboratory, Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu 603203, India
| | - Arikketh Devi
- Cancer and Stem Cell Biology Laboratory, Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu 603203, India
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10
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Liu N, Yao N, Wang S, Zhang Z, Ren T, Gao Y, Zhou X, Tong L, Zhang L. An optical nanofibre-enabled on-chip single-nanoparticle sensor. LAB ON A CHIP 2023; 23:4901-4908. [PMID: 37874569 DOI: 10.1039/d3lc00499f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/25/2023]
Abstract
Single-nanoparticle detection has received tremendous interest due to its significance in fundamental physics and biological applications. Here, we demonstrate an optical nanofibre-enabled microfluidic sensor for the detection and sizing of nanoparticles. Benefitting from the strong evanescent field outside the nanofibre, a nanoparticle close to the nanofibre can scatter a portion of the field energy to the environment, resulting in a decrease in the transmitted intensity of the nanofibre. On the other hand, the narrow and shallow microfluidic channel provides a femtoliter-scale detection region, making nanoparticles flow through the detection region one by one. By real-time monitoring of the transmitted intensity of the nanofibre, the detection of a single polystyrene (PS) nanoparticle as small as 100 nm in diameter and exosomes in solution is realised. Based on a statistical analysis, the mean scattering signal is related to the size of the nanoparticle. Experimentally, a mixture of nanoparticles of different diameters (200, 500, and 1000 nm) in solution is identified. To demonstrate its potential in biological applications, high-throughput counting of yeasts using a pair of microchannels and dual-wavelength detection of fluorescently labelled nanoparticles are realised. We believe that the developed nanoparticle sensor holds great potential for the multiplexed and rapid sensing of diverse viruses.
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Affiliation(s)
- Ning Liu
- State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, Zhejiang University, Hangzhou 310027, China.
| | - Ni Yao
- Research Center for Humanoid Sensing, Zhejiang Lab, Hangzhou 311121, China
| | - Shipeng Wang
- Research Center for Humanoid Sensing, Zhejiang Lab, Hangzhou 311121, China
| | - Zhang Zhang
- Research Center for Intelligent Robotics, Zhejiang Lab, Hangzhou 311121, China
| | - Tanchen Ren
- Department of Cardiology of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Ying Gao
- Department of Cardiology of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Xuhao Zhou
- Department of Cardiology of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Limin Tong
- State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, Zhejiang University, Hangzhou 310027, China.
| | - Lei Zhang
- State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, Zhejiang University, Hangzhou 310027, China.
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11
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Ranjan P, Colin K, Dutta RK, Verma SK. Challenges and future scope of exosomes in the treatment of cardiovascular diseases. J Physiol 2023; 601:4873-4893. [PMID: 36398654 PMCID: PMC10192497 DOI: 10.1113/jp282053] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 10/21/2022] [Indexed: 07/28/2023] Open
Abstract
Exosomes are nanosized vesicles that carry biologically diverse molecules for intercellular communication. Researchers have been trying to engineer exosomes for therapeutic purposes by using different approaches to deliver biologically active molecules to the various target cells efficiently. Recent technological advances may allow the biodistribution and pharmacokinetics of exosomes to be modified to meet scientific needs with respect to specific diseases. However, it is essential to determine an exosome's optimal dosage and potential side effects before its clinical use. Significant breakthroughs have been made in recent decades concerning exosome labelling and imaging techniques. These tools provide in situ monitoring of exosome biodistribution and pharmacokinetics and pinpoint targetability. However, because exosomes are nanometres in size and vary significantly in contents, a deeper understanding is required to ensure accurate monitoring before they can be applied in clinical settings. Different research groups have established different approaches to elucidate the roles of exosomes and visualize their spatial properties. This review covers current and emerging strategies for in vivo and in vitro exosome imaging and tracking for potential studies.
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Affiliation(s)
- Prabhat Ranjan
- Department of Medicine, Division of Cardiovascular Disease, The University of Alabama at Birmingham, Birmingham, AL-35233
| | - Karen Colin
- Department of Medicine, Division of Cardiovascular Disease, The University of Alabama at Birmingham, Birmingham, AL-35233
- UAB School of Health Professions, The University of Alabama at Birmingham, Birmingham, AL
| | - Roshan Kumar Dutta
- Department of Medicine, Division of Cardiovascular Disease, The University of Alabama at Birmingham, Birmingham, AL-35233
| | - Suresh Kumar Verma
- Department of Medicine, Division of Cardiovascular Disease, The University of Alabama at Birmingham, Birmingham, AL-35233
- Department of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, Alabama
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12
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Lan B, Dong X, Yang Q, Luo Y, Wen H, Chen Z, Chen H. Exosomal MicroRNAs: An Emerging Important Regulator in Acute Lung Injury. ACS OMEGA 2023; 8:35523-35537. [PMID: 37810708 PMCID: PMC10551937 DOI: 10.1021/acsomega.3c04955] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 09/11/2023] [Indexed: 10/10/2023]
Abstract
Acute lung injury (ALI) is a clinically life-threatening form of respiratory failure with a mortality of 30%-40%. Acute respiratory distress syndrome is the aggravated form of ALI. Exosomes are extracellular lipid vesicles ubiquitous in human biofluids with a diameter of 30-150 nm. They can serve as carriers to convey their internal cargo, particularly microRNA (miRNA), to the target cells involved in cellular communication. In disease states, the quantities of exosomes and the cargo generated by cells are altered. These exosomes subsequently function as autocrine or paracrine signals to nearby or distant cells, regulating various pathogenic processes. Moreover, exosomal miRNAs from multiple stem cells can provide therapeutic value for ALI by regulating different signaling pathways. In addition, changes in exosomal miRNAs of biofluids can serve as biomarkers for the early diagnosis of ALI. This study aimed to review the role of exosomal miRNAs produced by different sources participating in various pathological processes of ALI and explore their potential significance in the treatment and diagnosis.
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Affiliation(s)
- Bowen Lan
- Department
of General Surgery, The First Affiliated
Hospital of Dalian Medical University, Dalian 116000, China
- Laboratory
of Integrative Medicine, The First Affiliated
Hospital of Dalian Medical University, Dalian 116000, China
| | - Xuanchi Dong
- Department
of General Surgery, The First Affiliated
Hospital of Dalian Medical University, Dalian 116000, China
- Laboratory
of Integrative Medicine, The First Affiliated
Hospital of Dalian Medical University, Dalian 116000, China
| | - Qi Yang
- Department
of General Surgery, The First Affiliated
Hospital of Dalian Medical University, Dalian 116000, China
- Laboratory
of Integrative Medicine, The First Affiliated
Hospital of Dalian Medical University, Dalian 116000, China
- Department
of Traditional Chinese Medicine, The Second
Affiliated Hospital of Dalian Medical University, Dalian 116023, China
| | - Yalan Luo
- Department
of General Surgery, The First Affiliated
Hospital of Dalian Medical University, Dalian 116000, China
- Laboratory
of Integrative Medicine, The First Affiliated
Hospital of Dalian Medical University, Dalian 116000, China
- Institute
(College) of Integrative Medicine, Dalian
Medical University, Dalian 116044, China
| | - Haiyun Wen
- Department
of General Surgery, The First Affiliated
Hospital of Dalian Medical University, Dalian 116000, China
- Laboratory
of Integrative Medicine, The First Affiliated
Hospital of Dalian Medical University, Dalian 116000, China
- Institute
(College) of Integrative Medicine, Dalian
Medical University, Dalian 116044, China
| | - Zhe Chen
- Department
of General Surgery, The First Affiliated
Hospital of Dalian Medical University, Dalian 116000, China
- Laboratory
of Integrative Medicine, The First Affiliated
Hospital of Dalian Medical University, Dalian 116000, China
| | - Hailong Chen
- Department
of General Surgery, The First Affiliated
Hospital of Dalian Medical University, Dalian 116000, China
- Laboratory
of Integrative Medicine, The First Affiliated
Hospital of Dalian Medical University, Dalian 116000, China
- Institute
(College) of Integrative Medicine, Dalian
Medical University, Dalian 116044, China
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13
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Chen K, Duong BTV, Ahmed SU, Dhavarasa P, Wang Z, Labib M, Flynn C, Xu J, Zhang YY, Wang H, Yang X, Das J, Zargartalebi H, Ma Y, Kelley SO. A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles. Nat Commun 2023; 14:5576. [PMID: 37696888 PMCID: PMC10495366 DOI: 10.1038/s41467-023-41285-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Accepted: 08/30/2023] [Indexed: 09/13/2023] Open
Abstract
Exosomal PD-L1 (exoPD-L1) has recently received significant attention as a biomarker predicting immunotherapeutic responses involving the PD1/PD-L1 pathway. However, current technologies for exosomal analysis rely primarily on bulk measurements that do not consider the heterogeneity found within exosomal subpopulations. Here, we present a nanoscale cytometry platform NanoEPIC, enabling phenotypic sorting and exoPD-L1 profiling from blood plasma. We highlight the efficacy of NanoEPIC in monitoring anti-PD-1 immunotherapy through the interrogation of exoPD-L1. NanoEPIC generates signature exoPD-L1 patterns in responders and non-responders. In mice treated with PD1-targeted immunotherapy, exoPD-L1 is correlated with tumor growth, PD-L1 burden in tumors, and the immune suppression of CD8+ tumor-infiltrating lymphocytes. Small extracellular vesicles (sEVs) with different PD-L1 expression levels display distinctive inhibitory effects on CD8 + T cells. NanoEPIC offers robust, high-throughput profiling of exosomal markers, enabling sEV subpopulation analysis. This platform holds the potential for enhanced cancer screening, personalized treatment, and therapeutic response monitoring.
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Affiliation(s)
- Kangfu Chen
- Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada
| | - Bill T V Duong
- Department of Chemistry, University of Toronto, Toronto, ON, Canada
| | - Sharif U Ahmed
- Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada
| | | | - Zongjie Wang
- Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA
| | - Mahmoud Labib
- Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada
- Department of Chemistry, Northwestern University, Evanston, IL, USA
- Peninsula Medical School, Faculty of Health, University of Plymouth, Plymouth, UK
| | - Connor Flynn
- Department of Chemistry, University of Toronto, Toronto, ON, Canada
- Department of Chemistry, Northwestern University, Evanston, IL, USA
| | - Jingya Xu
- Department of Chemistry, University of Toronto, Toronto, ON, Canada
| | - Yi Y Zhang
- Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada
| | - Hansen Wang
- Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada
| | - Xiaolong Yang
- Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada
| | - Jagotamoy Das
- Department of Chemistry, Northwestern University, Evanston, IL, USA
| | - Hossein Zargartalebi
- Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada
| | - Yuan Ma
- Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada
| | - Shana O Kelley
- Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada.
- Department of Chemistry, University of Toronto, Toronto, ON, Canada.
- Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
- Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
- Department of Chemistry, Northwestern University, Evanston, IL, USA.
- Institute for Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
- Chan Zuckerberg Biohub Chicago, Chicago, IL, USA.
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14
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Tsunedomi R, Shindo Y, Nakajima M, Yoshimura K, Nagano H. The tumor immune microenvironment in pancreatic cancer and its potential in the identification of immunotherapy biomarkers. Expert Rev Mol Diagn 2023; 23:1121-1134. [PMID: 37947389 DOI: 10.1080/14737159.2023.2281482] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 11/06/2023] [Indexed: 11/12/2023]
Abstract
INTRODUCTION Pancreatic cancer (PC) has an extremely poor prognosis, even with surgical resection and triplet chemotherapy treatment. Cancer immunotherapy has been recently approved for tumor-agnostic treatment with genome analysis, including in PC. However, it has limited efficacy. AREAS COVERED In addition to the low tumor mutation burden, one of the difficulties of immunotherapy in PC is the presence of abundant stromal cells in its microenvironment. Among stromal cells, cancer-associated fibroblasts (CAFs) play a major role in immunotherapy resistance, and CAF-targeted therapies are currently under development, including those in combination with immunotherapies. Meanwhile, microbiomes and tumor-derived exosomes (TDEs) have been shown to alter the behavior of distant receptor cells in PC. This review discusses the role of CAFs, microbiomes, and TDEs in PC tumor immunity. EXPERT OPINION Elucidating the mechanisms by which CAFs, microbiomes, and TDEs are involved in the tumorigenesis of PC will be helpful for developing novel immunotherapeutic strategies and identifying companion biomarkers for immunotherapy. Spatial single-cell analysis of the tumor microenvironment will be useful for identifying biomarkers of PC immunity. Furthermore, given the complexity of immune mechanisms, artificial intelligence models will be beneficial for predicting the efficacy of immunotherapy.
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Affiliation(s)
- Ryouichi Tsunedomi
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Yoshitaro Shindo
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Masao Nakajima
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Kiyoshi Yoshimura
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo, Japan
- Department of Clinical Immuno-Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Setagaya, Tokyo, Japan
| | - Hiroaki Nagano
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
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15
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Zahid AA, Chakraborty A, Luo W, Coyle A, Paul A. Tailoring the Inherent Properties of Biobased Nanoparticles for Nanomedicine. ACS Biomater Sci Eng 2023. [PMID: 37378614 DOI: 10.1021/acsbiomaterials.3c00364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/29/2023]
Abstract
Biobased nanoparticles are at the leading edge of the rapidly developing field of nanomedicine and biotherapeutics. Their unique size, shape, and biophysical properties make them attractive tools for biomedical research, including vaccination, targeted drug delivery, and immune therapy. These nanoparticles are engineered to present native cell receptors and proteins on their surfaces, providing a biomimicking camouflage for therapeutic cargo to evade rapid degradation, immune rejection, inflammation, and clearance. Despite showing promising clinical relevance, commercial implementation of these biobased nanoparticles is yet to be fully realized. In this perspective, we discuss advanced biobased nanoparticle designs used in medical applications, such as cell membrane nanoparticles, exosomes, and synthetic lipid-derived nanoparticles, and highlight their benefits and potential challenges. Moreover, we critically assess the future of preparing such particles using artificial intelligence and machine learning. These advanced computational tools will be able to predict the functional composition and behavior of the proteins and cell receptors present on the nanoparticle surfaces. With more advancement in designing new biobased nanoparticles, this field of research could play a key role in dictating the future rational design of drug transporters, thereby ultimately improving overall therapeutic outcomes.
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Affiliation(s)
- Alap Ali Zahid
- Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, Ontario N6A 5B9, Canada
| | - Aishik Chakraborty
- Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, Ontario N6A 5B9, Canada
| | - Wei Luo
- Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, Ontario N6A 5B9, Canada
| | - Ali Coyle
- School of Biomedical Engineering, The University of Western Ontario, London, Ontario N6A 5B9, Canada
| | - Arghya Paul
- Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, Ontario N6A 5B9, Canada
- School of Biomedical Engineering, The University of Western Ontario, London, Ontario N6A 5B9, Canada
- Department of Chemistry, The Centre for Advanced Materials and Biomaterials Research, The University of Western Ontario, London, Ontario N6A 5B9, Canada
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16
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Pammi Guru KT, Praween N, Basu PK. Investigating the Electric Field Lysis of Exosomes Immobilized on the Screen-Printed Electrode and Electrochemical Sensing of the Lysed-Exosome-Derived Protein. BIOSENSORS 2023; 13:bios13030323. [PMID: 36979537 PMCID: PMC10046613 DOI: 10.3390/bios13030323] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 02/07/2023] [Accepted: 02/16/2023] [Indexed: 05/28/2023]
Abstract
It is important to isolate exosomes (<150 nm) from biofluid for diagnosis or prognosis purposes, followed by sensing of exosomal proteins. In the present work, exosomes are isolated from human serum by immobilizing on a Screen-Printed Electrode (SPE) followed by electric field lysis and electrochemical impedance spectroscopy (EIS)-based sensing of relevant exosomal proteins (HSP70 and HER2). Upon immobilization of exosomes on the surface, the role of different electrical signals (sinusoidal and square wave) in the lysis of exosomes was studied by varying the frequency and voltage. HSP70 was used for EIS to determine the optimal voltage and frequency for lysing the exosomes. It was observed that the low frequencies and, specifically, sinusoidal signals are ideal for lysing exosomes as compared to square signals. The relative quantity of HSP70 obtained by lysing with different voltages (sinusoidal waveform) was compared using Western blotting. After electric field lysis of the exosome with an optimized signal, HER2, a breast cancer biomarker, was detected successfully from serum by EIS. In the proposed technique, 3.5 × 108 exosomes/mL were isolated from serum. With the limit of detection of 10 pg, the designed cell showed a linear detection of HER2 from 0.1 ng to 1 µg. It was observed from the results that the electric field lysis of exosomes not only plays a significant role in releasing the cargo protein but also improves the sensing of surface proteins associated with exosomes.
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17
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Lo Faro MJ, Leonardi AA, Priolo F, Fazio B, Irrera A. Future Prospects of Luminescent Silicon Nanowires Biosensors. BIOSENSORS 2022; 12:1052. [PMID: 36421170 PMCID: PMC9688548 DOI: 10.3390/bios12111052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/15/2022] [Accepted: 11/17/2022] [Indexed: 06/16/2023]
Abstract
In this paper, we exploit the perspective of luminescent Si nanowires (NWs) in the growing field of commercial biosensing nanodevices for the selective recognition of proteins and pathogen genomes. We fabricated quantum confined fractal arrays of Si NWs with room temperature emission at 700 nm obtained by thin-film, metal-assisted, chemical etching with high production output at low cost. The fascinating optical features arising from multiple scattering and weak localization of light promote the use of Si NWs as optical biosensing platforms with high sensitivity and selectivity. In this work, label-free Si NW optical sensors are surface modified for the selective detection of C-reactive protein through antigen-gene interaction. In this case, we report the lowest limit of detection (LOD) of 1.6 fM, fostering the flexibility of different dynamic ranges for detection either in saliva or for serum analyses. By varying the NW surface functionalization with the specific antigen, the luminescence quenching of NW biosensors is used to measure the hepatitis B-virus pathogen genome without PCR-amplification, with an LOD of about 20 copies in real samples or blood matrix. The promising results show that NW optical biosensors can detect and isolate extracellular vesicles (EV) marked with CD81 protein with unprecedented sensitivity (LOD 2 × 105 sEV/mL), thus enabling their measurement even in a small amount of blastocoel fluid.
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Affiliation(s)
- Maria Josè Lo Faro
- Department of Physics and Astronomy, University of Catania, Via Santa Sofia 64, 95123 Catania, Italy
- CNR-IMM UoS Catania, Via Santa Sofia 64, 95123 Catania, Italy
| | - Antonio Alessio Leonardi
- Department of Physics and Astronomy, University of Catania, Via Santa Sofia 64, 95123 Catania, Italy
- CNR-IMM UoS Catania, Via Santa Sofia 64, 95123 Catania, Italy
| | - Francesco Priolo
- Department of Physics and Astronomy, University of Catania, Via Santa Sofia 64, 95123 Catania, Italy
| | - Barbara Fazio
- URT LAB SENS, Beyond Nano—CNR, c/o Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres 5, 98166 Messina, Italy
| | - Alessia Irrera
- URT LAB SENS, Beyond Nano—CNR, c/o Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres 5, 98166 Messina, Italy
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18
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19
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Yang Q, Luo Y, Lan B, Dong X, Wang Z, Ge P, Zhang G, Chen H. Fighting Fire with Fire: Exosomes and Acute Pancreatitis-Associated Acute Lung Injury. Bioengineering (Basel) 2022; 9:615. [PMID: 36354526 PMCID: PMC9687423 DOI: 10.3390/bioengineering9110615] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 10/18/2022] [Accepted: 10/24/2022] [Indexed: 08/30/2023] Open
Abstract
Acute pancreatitis (AP) is a prevalent clinical condition of the digestive system, with a growing frequency each year. Approximately 20% of patients suffer from severe acute pancreatitis (SAP) with local consequences and multi-organ failure, putting a significant strain on patients' health insurance. According to reports, the lungs are particularly susceptible to SAP. Acute respiratory distress syndrome, a severe type of acute lung injury (ALI), is the primary cause of mortality among AP patients. Controlling the mortality associated with SAP requires an understanding of the etiology of AP-associated ALI, the discovery of biomarkers for the early detection of ALI, and the identification of potentially effective drug treatments. Exosomes are a class of extracellular vesicles with a diameter of 30-150 nm that are actively released into tissue fluids to mediate biological functions. Exosomes are laden with bioactive cargo, such as lipids, proteins, DNA, and RNA. During the initial stages of AP, acinar cell-derived exosomes suppress forkhead box protein O1 expression, resulting in M1 macrophage polarization. Similarly, macrophage-derived exosomes activate inflammatory pathways within endothelium or epithelial cells, promoting an inflammatory cascade response. On the other hand, a part of exosome cargo performs tissue repair and anti-inflammatory actions and inhibits the cytokine storm during AP. Other reviews have detailed the function of exosomes in the development of AP, chronic pancreatitis, and autoimmune pancreatitis. The discoveries involving exosomes at the intersection of AP and acute lung injury (ALI) are reviewed here. Furthermore, we discuss the therapeutic potential of exosomes in AP and associated ALI. With the continuous improvement of technological tools, the research on exosomes has gradually shifted from basic to clinical applications. Several exosome-specific non-coding RNAs and proteins can be used as novel molecular markers to assist in the diagnosis and prognosis of AP and associated ALI.
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Affiliation(s)
- Qi Yang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China
| | - Yalan Luo
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Bowen Lan
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Xuanchi Dong
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Zhengjian Wang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Peng Ge
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Guixin Zhang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Hailong Chen
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116044, China
- Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
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20
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The distinct roles of exosomes in innate immune responses and therapeutic applications in cancer. Eur J Pharmacol 2022; 933:175292. [PMID: 36150532 DOI: 10.1016/j.ejphar.2022.175292] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 09/13/2022] [Accepted: 09/15/2022] [Indexed: 11/21/2022]
Abstract
The innate immune system is one of the major constituents of the host's defense against invading pathogens and extracellular vesicles (EVs) are involved in regulating its responses. Exosomes, a subclass of EVs, released from eukaryotic cells, contribute to intracellular communication and drive various biological processes by transferring nuclei acids, proteins, lipids, and carbohydrates between cells, protecting cargo from enzymatic degradation and immune recognition and consequent elimination by the immune system. A growing body of evidence has revealed that exosomes produced from host cells, infected cells, tumor cells, and immune cells regulate innate immune signaling and responses and thus play a significant role in the propagation of pathogens. Immune cells can recognize exosomes-bearing components including DNA strands, viral RNAs, and even proteins by various mechanisms such as through Toll-like receptor/NF-κB signaling, inducing cytokine production and reprogramming the innate immune responses, immunosuppression or immunesupportive. There is persuasive preclinical and clinical evidence that exosomes are therapeutic strategies for immunotherapy, cancer vaccine, drug-delivery system, and diagnostic biomarker. However, further scrutiny is essential to validate these findings. In this review, we describe the current facts on the regulation of innate immune responses by exosomes. We also describe the translational application of exosomes as cancer-therapy agents and immunotherapy.
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21
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An electrochemical biosensor for exosome detection based on covalent organic frameworks conjugated with DNA and horseradish peroxidase. J Electroanal Chem (Lausanne) 2022. [DOI: 10.1016/j.jelechem.2022.116576] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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22
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Theel EK, Schwaminger SP. Microfluidic Approaches for Affinity-Based Exosome Separation. Int J Mol Sci 2022; 23:ijms23169004. [PMID: 36012270 PMCID: PMC9409173 DOI: 10.3390/ijms23169004] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/09/2022] [Accepted: 08/10/2022] [Indexed: 12/13/2022] Open
Abstract
As a subspecies of extracellular vesicles (EVs), exosomes have provided promising results in diagnostic and theranostic applications in recent years. The nanometer-sized exosomes can be extracted by liquid biopsy from almost all body fluids, making them especially suitable for mainly non-invasive point-of-care (POC) applications. To achieve this, exosomes must first be separated from the respective biofluid. Impurities with similar properties, heterogeneity of exosome characteristics, and time-related biofouling complicate the separation. This practical review presents the state-of-the-art methods available for the separation of exosomes. Furthermore, it is shown how new separation methods can be developed. A particular focus lies on the fabrication and design of microfluidic devices using highly selective affinity separation. Due to their compactness, quick analysis time and portable form factor, these microfluidic devices are particularly suitable to deliver fast and reliable results for POC applications. For these devices, new manufacturing methods (e.g., laminating, replica molding and 3D printing) that use low-cost materials and do not require clean rooms are presented. Additionally, special flow routes and patterns that increase contact surfaces, as well as residence time, and thus improve affinity purification are displayed. Finally, various analyses are shown that can be used to evaluate the separation results of a newly developed device. Overall, this review paper provides a toolbox for developing new microfluidic affinity devices for exosome separation.
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Affiliation(s)
- Eike K. Theel
- Bioseparation Engineering Group, School of Engineering and Design, Technical University of Munich, Boltzmannstraße 15, 85748 Garching bei München, Germany
| | - Sebastian P. Schwaminger
- Bioseparation Engineering Group, School of Engineering and Design, Technical University of Munich, Boltzmannstraße 15, 85748 Garching bei München, Germany
- Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz, Neue Stiftingtalstraße 6, 8010 Graz, Austria
- Correspondence:
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23
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Zhang W, Wang L, Li D, Campbell DH, Walsh BJ, Packer NH, Dong Q, Wang E, Wang Y. Phenotypic profiling of pancreatic ductal adenocarcinoma plasma-derived small extracellular vesicles for cancer diagnosis and cancer stage prediction: a proof-of-concept study. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2022; 14:2255-2265. [PMID: 35612592 DOI: 10.1039/d2ay00536k] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Circulating pancreatic ductal adenocarcinoma (PDAC) derived small extracellular vesicles (sEVs) are nano-sized membranous vesicles secreted from PDAC cells and released into surrounding body fluids, such as blood. The use of plasma-derived sEVs for cancer diagnosis is particularly appealing in biomedical research because the sEVs reflect some key features (e.g. genetic and phenotypic status) related to the organs from which they originate. For example, the surface membrane proteins and their expression level on sEVs were reported to be related to the presence and progression of PDAC. However, difficulty in sEVs isolation and lack of ultrasensitive assays for simultaneous analysis of multiple protein biomarkers on patient plasma-derived sEVs hinder their application in the clinic. In our previous study, we have demonstrated the application of magnetic beads (MBs) and surface-enhanced Raman scattering (SERS) assay for phenotypic analysis of cancer cells-derived sEVs using different cell lines. To further demonstrate the clinical application of the proposed assay, we have profiled the sEVs' phenotypes (relative expression of biomarker Glypican 1, EpCAM and CD44V6) of healthy donors and PDAC patients to enable simultaneous detection of multiple surface membrane proteins on plasma-derived sEVs. We discovered that the PDAC sEVs' phenotype signatures had high accuracy for PDAC diagnosis (100%) and showed strong correlation with cancer stages, which were further validated by the imaging techniques (e.g. computerized tomography and magnetic resonance imaging) and also the correlation of cancer stages with CA19-9 (gold standard biomarker) and the sEVs' phenotype signatures. The present proof-of-concept study thus provides an initial investigation of using the proposed SERS assay for PDAC diagnosis and early cancer stage prediction in the clinic.
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Affiliation(s)
- Wei Zhang
- ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), School of Natural Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW 2109, Australia.
| | - Ling Wang
- Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun 130041, Jilin, P. R. China
| | - Dan Li
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, Jilin, P. R. China.
| | | | - Bradley J Walsh
- Minomic International Ltd, Macquarie Park, NSW 2113, Australia
| | - Nicolle H Packer
- ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), School of Natural Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW 2109, Australia.
| | - Qing Dong
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, Jilin, P. R. China.
| | - Erkang Wang
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, Jilin, P. R. China.
| | - Yuling Wang
- ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), School of Natural Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW 2109, Australia.
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24
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Zhang X, Wu Y, Cheng Q, Bai L, Huang S, Gao J. Extracellular Vesicles in Cardiovascular Diseases: Diagnosis and Therapy. Front Cell Dev Biol 2022; 10:875376. [PMID: 35721498 PMCID: PMC9198246 DOI: 10.3389/fcell.2022.875376] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 05/13/2022] [Indexed: 12/20/2022] Open
Abstract
Cardiovascular diseases (CVDs) are the leading cause of global mortality. Therapy of CVDs is still a great challenge since many advanced therapies have been developed. Multiple cell types produce nano-sized extracellular vesicles (EVs), including cardiovascular system-related cells and stem cells. Compelling evidence reveals that EVs are associated with the pathophysiological processes of CVDs. Recently researches focus on the clinical transformation in EVs-based diagnosis, prognosis, therapies, and drug delivery systems. In this review, we firstly discuss the current knowledge about the biophysical properties and biological components of EVs. Secondly, we will focus on the functions of EVs on CVDs, and outline the latest advances of EVs as prognostic and diagnostic biomarkers, and therapeutic agents. Finally, we will introduce the specific application of EVs as a novel drug delivery system and its application in CVDs therapy. Specific attention will be paid to summarize the perspectives, challenges, and applications on EVs’ clinical and industrial transformation.
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Affiliation(s)
- Xiaojing Zhang
- Department of Pharmacy, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, China
- *Correspondence: Xiaojing Zhang, ; Jun Gao,
| | - Yuping Wu
- Department of Scientific Research, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, China
| | - Qifa Cheng
- Department of Pharmacy, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, China
| | - Liyang Bai
- Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, China
| | - Shuqiang Huang
- Department of Clinical Medicine, The Sixth Clinical School of Guangzhou Medical University, Guangzhou, China
| | - Jun Gao
- Department of Pharmacy, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, China
- *Correspondence: Xiaojing Zhang, ; Jun Gao,
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25
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Zhao L, Wang H, Fu J, Wu X, Liang XY, Liu XY, Wu X, Cao LL, Xu ZY, Dong M. Microfluidic-based exosome isolation and highly sensitive aptamer exosome membrane protein detection for lung cancer diagnosis. Biosens Bioelectron 2022; 214:114487. [DOI: 10.1016/j.bios.2022.114487] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 05/28/2022] [Accepted: 06/14/2022] [Indexed: 11/29/2022]
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26
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Mazouzi Y, Sallem F, Farina F, Loiseau A, Tartaglia NR, Fontaine M, Parikh A, Salmain M, Neri C, Boujday S. Biosensing Extracellular Vesicle Subpopulations in Neurodegenerative Disease Conditions. ACS Sens 2022; 7:1657-1665. [PMID: 35446554 DOI: 10.1021/acssensors.1c02658] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Extracellular vesicles (EVs) are secreted nanoparticles that are involved in intercellular communication and that modulate a wide range of biological processes in normal and disease conditions. However, EVs are highly heterogeneous in terms of origin in the cell, size, and density. As a result, complex protocols are required to identify and characterize specific EV subpopulations, limiting biomedical applications, notably in diagnostics. Here, we show that combining quartz crystal microbalance with dissipation (QCM-D) and nanoplasmonic sensing (NPS) provides a facile method to track the viscoelastic properties of small EVs. We applied this multisensing strategy to analyze small EVs isolated by differential ultracentrifugation from knock-in mouse striatal cells expressing either a mutated allele or wild-type allele of huntingtin (Htt), the Huntington's disease gene. Our results validate the sensing strategy coupling QCM-D and NPS and suggest that the mass and viscoelastic dissipation of EVs can serve as potent biomarkers for sensing the intercellular changes associated with the neurodegenerative condition.
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Affiliation(s)
- Yacine Mazouzi
- Sorbonne Université, CNRS, Laboratoire de Réactivité de Surface (LRS), 75005 Paris, France
| | - Fadoua Sallem
- Sorbonne Université, CNRS, Laboratoire de Réactivité de Surface (LRS), 75005 Paris, France
| | - Francesca Farina
- CNRS UMR 8256, ERL INSERM U1164, Sorbonne Université, 75005 Paris, France
| | - Alexis Loiseau
- Sorbonne Université, CNRS, Laboratoire de Réactivité de Surface (LRS), 75005 Paris, France
| | | | - Morgane Fontaine
- CNRS UMR 8256, ERL INSERM U1164, Sorbonne Université, 75005 Paris, France
| | - Atul Parikh
- Sorbonne Université, CNRS, Laboratoire de Réactivité de Surface (LRS), 75005 Paris, France
- Biomedical Engineering, University of California Davis, Davis, California 95616, United States
| | - Michèle Salmain
- Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire (IPCM), 75005 Paris, France
| | - Christian Neri
- CNRS UMR 8256, ERL INSERM U1164, Sorbonne Université, 75005 Paris, France
| | - Souhir Boujday
- Sorbonne Université, CNRS, Laboratoire de Réactivité de Surface (LRS), 75005 Paris, France
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27
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Campos-Silva C, Cáceres-Martell Y, Sánchez-Herrero E, Sandúa A, Beneitez-Martínez A, González Á, Provencio M, Romero A, Jara-Acevedo R, Yáñez-Mó M, Valés-Gómez M. A simple immunoassay for extracellular vesicle liquid biopsy in microliters of non-processed plasma. J Nanobiotechnology 2022; 20:72. [PMID: 35135541 PMCID: PMC8822649 DOI: 10.1186/s12951-022-01256-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 01/09/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Extracellular vesicles (EVs), released by most cell types, provide an excellent source of biomarkers in biological fluids. However, in order to perform validation studies and screenings of patient samples, it is still necessary to develop general techniques permitting rapid handling of small amounts of biological samples from large numbers of donors. RESULTS Here we describe a method that, using just a few microliters of patient's plasma, identifies tumour markers exposed on EVs. Studying physico-chemical properties of EVs in solution, we demonstrate that they behave as stable colloidal suspensions and therefore, in immunocapture assays, many of them are unable to interact with a stationary functionalised surface. Using flocculation methods, like those used to destabilize colloids, we demonstrate that cationic polymers increase EV ζ-potential, diameter, and sedimentation coefficient and thus, allow a more efficient capture on antibody-coated surfaces by both ELISA and bead-assisted flow cytometry. These findings led to optimization of a protocol in microtiter plates allowing effective immunocapture of EVs, directly in plasma without previous ultracentrifugation or other EV enrichment. The method, easily adaptable to any laboratory, has been validated using plasma from lung cancer patients in which the epithelial cell marker EpCAM has been detected on EVs. CONCLUSIONS This optimized high throughput, easy to automate, technology allows screening of large numbers of patients to phenotype tumour markers in circulating EVs, breaking barriers for the validation of proposed EV biomarkers and the discovery of new ones.
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Affiliation(s)
- Carmen Campos-Silva
- Department of Immunology and Oncology, Spanish National Centre for Biotechnology, CNB-CSIC, Madrid, Spain
| | - Yaiza Cáceres-Martell
- Department of Immunology and Oncology, Spanish National Centre for Biotechnology, CNB-CSIC, Madrid, Spain
| | - Estela Sánchez-Herrero
- Laboratorio de Biopsia Líquida, Instituto de Investigación Sanitaria Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain.,Atrys Health, Barcelona, Spain
| | - Amaia Sandúa
- Service of Biochemistry, Clínica Universidad de Navarra, Pamplona, Spain
| | | | - Álvaro González
- Service of Biochemistry, Clínica Universidad de Navarra, Pamplona, Spain
| | - Mariano Provencio
- Laboratorio de Biopsia Líquida, Instituto de Investigación Sanitaria Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain.,Medical Oncology Department, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
| | - Atocha Romero
- Laboratorio de Biopsia Líquida, Instituto de Investigación Sanitaria Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain.,Medical Oncology Department, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain
| | | | - María Yáñez-Mó
- Department of Molecular Biology, UAM - Centro de Biología Molecular Severo Ochoa, Madrid, Spain.,Instituto de Investigación del Hospital Universitario La Princesa, Madrid, Spain
| | - Mar Valés-Gómez
- Department of Immunology and Oncology, Spanish National Centre for Biotechnology, CNB-CSIC, Madrid, Spain.
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28
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Leonardi AA, Battaglia R, Morganti D, Lo Faro MJ, Fazio B, De Pascali C, Francioso L, Palazzo G, Mallardi A, Purrello M, Priolo F, Musumeci P, Di Pietro C, Irrera A. A Novel Silicon Platform for Selective Isolation, Quantification, and Molecular Analysis of Small Extracellular Vesicles. Int J Nanomedicine 2021; 16:5153-5165. [PMID: 34611399 PMCID: PMC8487288 DOI: 10.2147/ijn.s310896] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 05/20/2021] [Indexed: 12/11/2022] Open
Abstract
Introduction Small extracellular vesicles (sEVs), thanks to their cargo, are involved in cellular communication and play important roles in cell proliferation, growth, differentiation, apoptosis, stemness and embryo development. Their contribution to human pathology has been widely demonstrated and they are emerging as strategic biomarkers of cancer, neurodegenerative and cardiovascular diseases, and as potential targets for therapeutic intervention. However, the use of sEVs for medical applications is still limited due to the selectivity and sensitivity limits of the commonly applied approaches. Methods Novel sensing solutions based on nanomaterials are arising as strategic tools able to surpass traditional sensor limits. Among these, Si nanowires (Si NWs), realized with cost-effective industrially compatible metal-assisted chemical etching, are perfect candidates for sEV detection. Results In this paper, the realization of a selective sensor able to isolate, concentrate and quantify specific vesicle populations, from minimal volumes of biofluid, is presented. In particular, this Si NW platform has a detection limit of about 2×105 sEVs/mL and was tested with follicular fluid and blastocoel samples. Moreover, the possibility to detach the selectively isolated sEVs allowing further analyses with other approaches was demonstrated by SEM analysis and several PCRs performed on the RNA content of the detached sEVs. Discussion This platform overcomes the limit of detection of traditional methods and, most importantly, preserves the biological content of sEVs, opening the route toward a reliable liquid biopsy analysis.
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Affiliation(s)
- Antonio Alessio Leonardi
- Dipartimento di Fisica e Astronomia, Università di Catania, Catania, 95123, Italy.,CNR-IPCF, Istituto per i Processi Chimico-Fisici, Messina, 98158, Italy.,CNR-IMM UoS Catania, Istituto per la Microelettronica e Microsistemi, Catania, 95123, Italy
| | - Rosalia Battaglia
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Dario Morganti
- Dipartimento di Fisica e Astronomia, Università di Catania, Catania, 95123, Italy.,CNR-IPCF, Istituto per i Processi Chimico-Fisici, Messina, 98158, Italy
| | - Maria Josè Lo Faro
- Dipartimento di Fisica e Astronomia, Università di Catania, Catania, 95123, Italy.,CNR-IMM UoS Catania, Istituto per la Microelettronica e Microsistemi, Catania, 95123, Italy
| | - Barbara Fazio
- CNR-IPCF, Istituto per i Processi Chimico-Fisici, Messina, 98158, Italy
| | - Chiara De Pascali
- CNR-IMM, Institute for Microelectronics and Microsystems, Via Monteroni, University Campus, Lecce, 73100, Italy
| | - Luca Francioso
- CNR-IMM, Institute for Microelectronics and Microsystems, Via Monteroni, University Campus, Lecce, 73100, Italy
| | - Gerardo Palazzo
- Chemistry Department, University of Bari 'Aldo Moro', Bari, 70125, Italy.,CSGI, Center for Colloid and Surface Science c/o Chemistry Department, Bari, 70125, Italy
| | - Antonia Mallardi
- CNR-IPCF, Institute for Chemical-Physical Processes, c/o Chemistry Department, Bari, 70125, Italy
| | - Michele Purrello
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Francesco Priolo
- Dipartimento di Fisica e Astronomia, Università di Catania, Catania, 95123, Italy
| | - Paolo Musumeci
- Dipartimento di Fisica e Astronomia, Università di Catania, Catania, 95123, Italy
| | - Cinzia Di Pietro
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Alessia Irrera
- CNR-IPCF, Istituto per i Processi Chimico-Fisici, Messina, 98158, Italy
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29
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Thakur A, Xu C, Li WK, Qiu G, He B, Ng SP, Wu CML, Lee Y. 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; 191:113476. [PMID: 34246124 DOI: 10.1016/j.bios.2021.113476] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 06/24/2021] [Accepted: 06/29/2021] [Indexed: 02/08/2023]
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.
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Affiliation(s)
- Abhimanyu Thakur
- Department of Neuroscience, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, SAR, China
| | - Chen Xu
- Department of Materials Science and Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, SAR, China
| | - Wing Kar Li
- Department of Biomedical Sciences, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, SAR, China
| | - Guangyu Qiu
- 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
| | - Bing He
- Department of Neuroscience, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, SAR, China
| | - Siu-Pang Ng
- Rafael Biotechnology Company Ltd., SAR, China
| | - Chi-Man Lawrence Wu
- Department of Materials Science and Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, SAR, China.
| | - Youngjin Lee
- Department of Neuroscience, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, SAR, China.
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30
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Singh K, Nalabotala R, Koo KM, Bose S, Nayak R, Shiddiky MJA. Separation of distinct exosome subpopulations: isolation and characterization approaches and their associated challenges. Analyst 2021; 146:3731-3749. [PMID: 33988193 DOI: 10.1039/d1an00024a] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Exosomes are nano-sized extracellular vesicles that serve as a communications system between cells and have shown tremendous promise as liquid biopsy biomarkers in diagnostic, prognostic, and even therapeutic use in different human diseases. Due to the natural heterogeneity of exosomes, there is a need to separate exosomes into distinct biophysical and/or biochemical subpopulations to enable full interrogation of exosome biology and function prior to the possibility of clinical translation. Currently, there exists a multitude of different exosome isolation and characterization approaches which can, in limited capacity, separate exosomes based on biophysical and/or biochemical characteristics. While notable reviews in recent years have reviewed these approaches for bulk exosome sorting, we herein present a comprehensive overview of various conventional technologies and modern microfluidic and nanotechnological advancements towards isolation and characterization of exosome subpopulations. The benefits and limitations of these different technologies to improve their use for distinct exosome subpopulations in clinical practices are also discussed. Furthermore, an overview of the most commonly encountered technical and biological challenges for effective separation of exosome subpopulations is presented.
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Affiliation(s)
- Karishma Singh
- Amity Institute of Nanotechnology, Amity University Uttar Pradesh, Noida 201301, UP, India.
| | - Ruchika Nalabotala
- Amity Institute of Nanotechnology, Amity University Uttar Pradesh, Noida 201301, UP, India.
| | - Kevin M Koo
- The University of Queensland Centre for Clinical Research (UQCCR), Herston, QLD 4029, Australia.
| | - Sudeep Bose
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida 201301, UP, India
| | - Ranu Nayak
- Amity Institute of Nanotechnology, Amity University Uttar Pradesh, Noida 201301, UP, India.
| | - Muhammad J A Shiddiky
- School of Environment and Natural Sciences and Queensland Micro- and Nanotechnology Centre, Griffith University, Nathan, QLD 4111, Australia.
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31
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Ullah M, Qian NPM, Yannarelli G. Advances in innovative exosome-technology for real time monitoring of viable drugs in clinical translation, prognosis and treatment response. Oncotarget 2021; 12:1029-1031. [PMID: 34084276 PMCID: PMC8169069 DOI: 10.18632/oncotarget.27927] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Indexed: 02/07/2023] Open
Affiliation(s)
- Mujib Ullah
- Correspondence to:Mujib Ullah, Institute for Immunity and Transplantation, Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Palo Alto, California 94304, USA email
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32
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Chen Y, Xu Y, Zhong H, Yuan H, Liang F, Liu J, Tang W. Extracellular vesicles in Inter-Kingdom communication in gastrointestinal cancer. Am J Cancer Res 2021; 11:1087-1103. [PMID: 33948347 PMCID: PMC8085842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 02/13/2021] [Indexed: 06/12/2023] Open
Abstract
The production and secretion of extracellular vesicles (EVs) are common features of cells (including various normal cells, neoplastic cell lines as well as bacteria) that span all domains of life. Tumor-derived exosomes are enriched with kinds of tumorigenesis mediators which are derived from the cytoplasm of cancer cells and fully reflect the tumor conditions. Indeed, the major topics and challenges on current oncological research are the identification of tumorigenic and metastatic molecules in tumor-cell-derived exosomes as well as elucidating the pathways that guarantee these components to be included in exosomes. The bacterial EVs have also been implicated in the pathogenesis of gastrointestinal (GI) tumors and chronic inflammatory diseases; however, the possible function of outer membrane vesicles (OMVs) in tumorigenesis remains largely underestimated. We suggest that EVs from both eukaryotic cells and different microbes in GI tract act as regulators of intracellular and cross-species communication, thus particularly facilitate tumor cell survival and multi-drug resistance. Therefore, our review introduces comprehensive knowledge on the promising role of EVs (mainly exosomes and OMVs) production of GI cancer development and gut microbiome, as well as its roles in developing novel therapeutic strategies.
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Affiliation(s)
- Yi Chen
- Department of Gastrointestinal Surgery, Division of Colorectal & Anal Surgery Guangxi Medical University Cancer HospitalNanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
- Guangxi Clinical Research Center for Colorectal CancerNanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
| | - Yansong Xu
- Department of Gastrointestinal Surgery, Division of Colorectal & Anal Surgery Guangxi Medical University Cancer HospitalNanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
- Guangxi Clinical Research Center for Colorectal CancerNanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
- Department of Emergency, The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021, Guangxi, P. R. China
| | - Huage Zhong
- Department of Gastrointestinal Surgery, Division of Colorectal & Anal Surgery Guangxi Medical University Cancer HospitalNanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
- Guangxi Clinical Research Center for Colorectal CancerNanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
| | - Hao Yuan
- Department of Gastrointestinal Surgery, Division of Colorectal & Anal Surgery Guangxi Medical University Cancer HospitalNanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
- Guangxi Clinical Research Center for Colorectal CancerNanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
| | - Fangfang Liang
- Department of Gastrointestinal Surgery, Division of Colorectal & Anal Surgery Guangxi Medical University Cancer HospitalNanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
- Guangxi Clinical Research Center for Colorectal CancerNanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021, Guangxi, P. R. China
| | - Junjie Liu
- Department of Gastrointestinal Surgery, Division of Colorectal & Anal Surgery Guangxi Medical University Cancer HospitalNanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
- Guangxi Clinical Research Center for Colorectal CancerNanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
- Department of Ultrasound, Guangxi Medical University Cancer HospitalNanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
| | - Weizhong Tang
- Department of Gastrointestinal Surgery, Division of Colorectal & Anal Surgery Guangxi Medical University Cancer HospitalNanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
- Guangxi Clinical Research Center for Colorectal CancerNanning 530021, Guangxi Zhuang Autonomous Region, P. R. China
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33
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Wang J, Ma P, Kim DH, Liu BF, Demirci U. Towards Microfluidic-Based Exosome Isolation and Detection for Tumor Therapy. NANO TODAY 2021; 37:101066. [PMID: 33777166 PMCID: PMC7990116 DOI: 10.1016/j.nantod.2020.101066] [Citation(s) in RCA: 131] [Impact Index Per Article: 32.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/09/2023]
Abstract
Exosomes are a class of cell-secreted, nano-sized extracellular vesicles with a bilayer membrane structure of 30-150 nm in diameter. Their discovery and application have brought breakthroughs in numerous areas, such as liquid biopsies, cancer biology, drug delivery, immunotherapy, tissue repair, and cardiovascular diseases. Isolation of exosomes is the first step in exosome-related research and its applications. Standard benchtop exosome separation and sensing techniques are tedious and challenging, as they require large sample volumes, multi-step operations that are complex and time-consuming, requiring cumbersome and expensive instruments. In contrast, microfluidic platforms have the potential to overcome some of these limitations, owing to their high-precision processing, ability to handle liquids at a microscale, and integrability with various functional units, such as mixers, actuators, reactors, separators, and sensors. These platforms can optimize the detection process on a single device, representing a robust and versatile technique for exosome separation and sensing to attain high purity and high recovery rates with a short processing time. Herein, we overview microfluidic strategies for exosome isolation based on their hydrodynamic properties, size filtration, acoustic fields, immunoaffinity, and dielectrophoretic properties. We focus especially on advances in label-free isolation of exosomes with active biological properties and intact morphological structures. Further, we introduce microfluidic techniques for the detection of exosomal proteins and RNAs with high sensitivity, high specificity, and low detection limits. We summarize the biomedical applications of exosome-mediated therapeutic delivery targeting cancer cells. To highlight the advantages of microfluidic platforms, conventional techniques are included for comparison. Future challenges and prospects of microfluidics towards exosome isolation applications are also discussed. Although the use of exosomes in clinical applications still faces biological, technical, regulatory, and market challenges, in the foreseeable future, recent developments in microfluidic technologies are expected to pave the way for tailoring exosome-related applications in precision medicine.
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Affiliation(s)
- Jie Wang
- Canary Center at Stanford for Cancer Early Detection, Bio-Acoustic MEMS in Medicine (BAMM) Laboratory, Department of Radiology, School of Medicine Stanford University, Palo Alto, California 94304-5427, USA
- Canary Center at Stanford for Cancer Early Detection, Department of Radiology, Stanford University School of Medicine, Palo Alto, California 94305, USA
| | - Peng Ma
- Canary Center at Stanford for Cancer Early Detection, Bio-Acoustic MEMS in Medicine (BAMM) Laboratory, Department of Radiology, School of Medicine Stanford University, Palo Alto, California 94304-5427, USA
- Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China
- Canary Center at Stanford for Cancer Early Detection, Department of Radiology, Stanford University School of Medicine, Palo Alto, California 94305, USA
| | - Daniel H Kim
- Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California 95064, USA
- Canary Center at Stanford for Cancer Early Detection, Department of Radiology, Stanford University School of Medicine, Palo Alto, California 94305, USA
| | - Bi-Feng Liu
- Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China
| | - Utkan Demirci
- Canary Center at Stanford for Cancer Early Detection, Bio-Acoustic MEMS in Medicine (BAMM) Laboratory, Department of Radiology, School of Medicine Stanford University, Palo Alto, California 94304-5427, USA
- Canary Center at Stanford for Cancer Early Detection, Department of Radiology, Stanford University School of Medicine, Palo Alto, California 94305, USA
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34
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Ko J, Wang Y, Sheng K, Weitz DA, Weissleder R. Sequencing-Based Protein Analysis of Single Extracellular Vesicles. ACS NANO 2021; 15:5631-5638. [PMID: 33687214 PMCID: PMC8742254 DOI: 10.1021/acsnano.1c00782] [Citation(s) in RCA: 79] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/08/2023]
Abstract
Circulating extracellular vesicles (EVs)-biological nanomaterials shed from most mammalian cells-have emerged as promising biomarkers, drug delivery vesicles, and treatment modulators. While different types of vesicles are being explored for these applications, it is becoming clear that human EVs are quite heterogeneous even in homogeneous or monoclonal cell populations. Since it is the surface EV protein composition that will largely dictate their biological behavior, high-throughput single EV profiling methods are needed to better define EV subpopulations. Here, we present an antibody-based immunosequencing method that allows multiplexed measurement of protein molecules from individual nanometer-sized EVs. We use droplet microfluidics to compartmentalize and barcode individual EVs. The barcodes/antibody-DNA are then sequenced to determine protein composition. Using this highly sensitive technology, we detected specific proteins at the single EV level. We expect that this technology can be further adapted for multiplexed protein analysis of any nanoparticle.
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Affiliation(s)
- Jina Ko
- Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114, USA
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA
| | - Yongcheng Wang
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA
- John A. Paulson School of Engineering and Applied Sciences and Department of Physics, Harvard University, Cambridge, MA 02138, USA
- Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
| | - Kuanwei Sheng
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA
| | - David A. Weitz
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA
- John A. Paulson School of Engineering and Applied Sciences and Department of Physics, Harvard University, Cambridge, MA 02138, USA
| | - Ralph Weissleder
- Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114, USA
- Department of Systems Biology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02115, USA
- R. Weissleder, MD, PhD, Center for Systems Biology, Massachusetts General Hospital Research Institute, 185 Cambridge St, CPZN 5206, Boston, MA, 02114, 617-726-8226,
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Lin B, Lei Y, Wang J, Zhu L, Wu Y, Zhang H, Wu L, Zhang P, Yang C. Microfluidic-Based Exosome Analysis for Liquid Biopsy. SMALL METHODS 2021; 5:e2001131. [PMID: 34927834 DOI: 10.1002/smtd.202001131] [Citation(s) in RCA: 101] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 12/29/2020] [Indexed: 06/14/2023]
Abstract
Liquid biopsy offers non-invasive and real-time molecular profiling of individual patients, and is thus considered a revolutionary technology in precision medicine. Exosomes have been acknowledged as significant biomarkers in liquid biopsy, as they play a central role in cell-cell communication and are closely related to the pathogenesis of most human malignancies. Nevertheless, in biofluids exosomes always co-exist with other particles, and the cargo components of exosomes are highly heterogeneous. Thus, the isolation and molecular characterization of exosomes are still technically challenging. Microfluidics technology effectively addresses this challenge by virtue of its inherent advantages, such as precise manipulation of fluids, low consumption of samples and reagents, and a high level of integration. Recent advances in microfluidics allow in situ exosome capture and molecular detection with unprecedented selectivity and sensitivity. In this review, the state-of-the-art developments in microfluidics-based exosome research, including exosome isolation approaches and molecular detection strategies, with highlights of the characterization of exosomal biomarkers in cancer liquid biopsy is summarized. The major challenges are also discussed and some perspectives for the future directions of exosome-based liquid biopsy in microfluidic systems are presented.
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Affiliation(s)
- Bingqian Lin
- The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China
| | - Yanmei Lei
- Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Junxia Wang
- The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China
| | - Lin Zhu
- The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China
| | - Yuqi Wu
- The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China
| | - Huimin Zhang
- The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China
| | - Lingling Wu
- Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Peng Zhang
- Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Chaoyong Yang
- The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China
- Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
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Chen P, Wang L, Fan X, Ning X, Yu B, Ou C, Chen M. Targeted delivery of extracellular vesicles in heart injury. Am J Cancer Res 2021; 11:2263-2277. [PMID: 33500724 PMCID: PMC7797669 DOI: 10.7150/thno.51571] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Accepted: 11/18/2020] [Indexed: 12/20/2022] Open
Abstract
Extracellular vesicles (EVs) are nanoscale extracellular vesicles derived from endocytosis that are crucial to intercellular communication. EVs possess natural biocompatibility and stability that allow them to cross biological membranes and that protect them from degradation. Recent studies have shown that EVs-mediated crosstalk between different cell types in the heart could play important roles in the maintenance of cardiac homeostasis and the pathogenesis of heart diseases. In particular, EVs secreted by different types of stem cells exhibit cardioprotective effects. However, numerous studies have shown that intravenously injected EVs are quickly cleared by macrophages of the mononuclear phagocyte system (MPS) and preferentially accumulate in MPS organs such as the liver, spleen, and lung. In this review, we discuss exosome biogenesis, the role of EVs in heart diseases, and challenges in delivering EVs to the heart. Furthermore, we extensively discuss the targeted delivery of EVs for treating ischemic heart disease. These understandings will aid in the development of effective treatment strategies for heart diseases.
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Hao N, Pei Z, Liu P, Bachman H, Naquin TD, Zhang P, Zhang J, Shen L, Yang S, Yang K, Zhao S, Huang TJ. Acoustofluidics-Assisted Fluorescence-SERS Bimodal Biosensors. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2020; 16:e2005179. [PMID: 33174375 PMCID: PMC7902458 DOI: 10.1002/smll.202005179] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Revised: 09/29/2020] [Indexed: 05/23/2023]
Abstract
Acoustofluidics, the fusion of acoustics and microfluidic techniques, has recently seen increased research attention across multiple disciplines due in part to its capabilities in contactless, biocompatible, and precise manipulation of micro-/nano-objects. Herein, a bimodal signal amplification platform which relies on acoustofluidics-induced enrichment of nanoparticles is introduced. The dual-function biosensor can perform sensitive immunofluorescent or surface-enhanced Raman spectroscopy (SERS) detection. The platform functions by using surface acoustic waves to concentrate nanoparticles at either the center or perimeter of a glass capillary; the concentration location is adjusted simply by varying the input frequency. The immunofluorescence assay is achieved by concentrating fluorescent analytes and functionalized nanoparticles at the center of the microchannel, thereby improving the visibility of the fluorescent output. By modifying the inner wall of the glass capillary with plasmonic Ag nanoparticle-deposited ZnO nanorod arrays and focusing analytes toward the perimeter of the microchannel, SERS sensing using the same device setup is achieved. Nanosized exosomes are used as a proof-of-concept to validate the performance of the acoustofluidic bimodal biosensor. With its sample-enrichment functionality, bimodal sensing, short processing time, and minute sample consumption, the acoustofluidic chip holds great potential for the development of lab-on-a-chip based analysis systems in many real-world applications.
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Affiliation(s)
- Nanjing Hao
- Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA
| | - Zhichao Pei
- Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA
| | - Pengzhan Liu
- Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA
| | - Hunter Bachman
- Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA
| | - Ty Downing Naquin
- Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA
| | - Peiran Zhang
- Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA
| | - Jinxin Zhang
- Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA
| | - Liang Shen
- Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA
| | - Shujie Yang
- Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA
| | - Kaichun Yang
- Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA
| | - Shuaiguo Zhao
- Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA
| | - Tony Jun Huang
- Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, 27708, USA
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Ferguson S, Weissleder R. Modeling EV Kinetics for Use in Early Cancer Detection. ADVANCED BIOSYSTEMS 2020; 4:e1900305. [PMID: 32394646 PMCID: PMC7658022 DOI: 10.1002/adbi.201900305] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Revised: 04/10/2020] [Accepted: 04/16/2020] [Indexed: 12/17/2022]
Abstract
Tumor-derived extracellular vesicles (EVs) represent promising biomarkers for monitoring cancers. Technological advances have improved the ability to measure EV reliably in blood using protein, RNA, or lipid detection methods. However, it is less clear how efficacious current EV assays are for the early detection of small and thus curable tumors. Here, a mathematical model is developed to estimate key parameter values and future requirements for EV testing. Tumor volumes in mice correlate well with increases in total number of circulating EV allowing the researchers to calculate EV shed rates for four different published cancer models. Model extrapolations to human physiology show good agreement with published clinical data. Specifically, it is shown that current bulk EV detection systems are ≈104 -fold too insensitive to detect human cancers of ≈1 cm3 . Conversely, it is predicted that emerging single EV methods will allow blood-based detection of cancers of <1 mm3 in humans.
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Affiliation(s)
- Scott Ferguson
- Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114
| | - Ralph Weissleder
- Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114
- Department of Systems Biology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02115
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Recent advances in nanomaterial-based biosensors for the detection of exosomes. Anal Bioanal Chem 2020; 413:83-102. [PMID: 33164151 DOI: 10.1007/s00216-020-03000-0] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 10/04/2020] [Accepted: 10/09/2020] [Indexed: 12/24/2022]
Abstract
Exosomes are a type of extracellular vesicle actively secreted by almost all eukaryotic cells. They are ideal candidates for reliable next-generation biomarkers in the early diagnosis and therapeutic response evaluation of cancer. Thus, the quantification of exosomes is crucial in facilitating clinical research and application. Compared with traditional materials, nanomaterials have better optical, magnetic, electrical, and catalytic properties due to their small size, high specific surface area, and variable structure. The incorporation of nanomaterials into sensing systems is an attractive approach towards improving sensitivity and can provide improved sensor selectivity and stability. In this paper, we summarize the progress in nanomaterial-based exosome detection methods, including electrochemical biosensors, photoelectrochemical biosensors, colorimetric biosensors, fluorescence biosensors, chemiluminescence biosensors, electrochemiluminescence biosensors, surface plasmon resonance biosensors, and surface-enhanced Raman spectroscopy biosensors. Moreover, future research directions and challenges in exosome detection methods are discussed. We hope that this article will offer an overview of nanomaterial-based exosome detection techniques and open new avenues in disease research.Graphical abstract.
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Zhou J, Wu Z, Hu J, Yang D, Chen X, Wang Q, Liu J, Dou M, Peng W, Wu Y, Wang W, Xie C, Wang M, Song Y, Zeng H, Bai C. High-throughput single-EV liquid biopsy: Rapid, simultaneous, and multiplexed detection of nucleic acids, proteins, and their combinations. SCIENCE ADVANCES 2020; 6:eabc1204. [PMID: 33219024 PMCID: PMC7679165 DOI: 10.1126/sciadv.abc1204] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 09/30/2020] [Indexed: 05/03/2023]
Abstract
MicroRNAs (miRNAs), mRNA, and proteins in/on extracellular vesicles (EVs) represent potential cancer biomarkers. Concurrent detection of multiple biomarkers at a single-EV level would greatly improve prognosis and/or diagnosis and understanding of EV phenotypes, biogenesis, and functions. Here, we introduced a High-throughput Nano-bio Chip Integrated System for Liquid Biopsy (HNCIB) system for simultaneous detection of proteins and mRNA/miRNA in a single EV. Validated through systematic control experiments, HNCIB showed high reliability, sensitivity, and specificity. In a panel of 34 patients with lung adenocarcinoma (LUAD) and 35 healthy donors, HNCIB detected an up-regulated expression of programmed death-ligand 1 mRNA and protein and miR-21 in EVs derived from patients with LUAD compared to those from healthy donors. HNCIB has low sample requirement (~90 μl), fast assay time (~6 hours), and high throughput (up to 384 samples per assay) and would have great potential in the study of EVs and their clinical applications.
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Affiliation(s)
- Jian Zhou
- Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zuoren Wu
- Hangzhou Dixiang Co. Ltd., Hangzhou, China
| | - Jie Hu
- Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Dawei Yang
- Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiaoyan Chen
- Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qin Wang
- Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jie Liu
- Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Maosen Dou
- Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wenjun Peng
- Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuanyuan Wu
- Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | | | | | - Ming Wang
- Hangzhou Dixiang Co. Ltd., Hangzhou, China
| | - Yuanlin Song
- Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | | | - Chunxue Bai
- Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
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Seledtsov VI, von Delwig A. Clinically feasible and prospective immunotherapeutic interventions in multidirectional comprehensive treatment of cancer. Expert Opin Biol Ther 2020; 21:323-342. [PMID: 32981358 DOI: 10.1080/14712598.2021.1828338] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION The immune system is able to exert both tumor-destructive and tumor-protective functions. Immunotherapeutic technologies aim to enhance immune-based anti-tumor activity and (or) weaken tumor-protective immunity. AREAS COVERED Cancer vaccination, antibody (Ab)-mediated cytotoxicity, Ab-based checkpoint molecule inhibition, Ab-based immunostimulation, cytokine therapy, oncoviral therapy, drug-mediated immunostimulation, exovesicular therapy, anti-inflammatory therapy, neurohormonal immunorehabilitation, metabolic therapy, as well as adoptive cell immunotherapy, could be coherently used to synergize and amplify each other in achieving robust anti-cancer responses in cancer patients. Tumor-specific immunotherapy applied at early stages is capable of eliminating remaining tumor cells after surgery, thus preventing the development of minimal residual disease. Patients with advanced disease stages could benefit from combined immunotherapy, which would be aimed at providing tumor cell/mass dormancy. Traditional therapeutic anti-cancer interventions (chemoradiotherapy, hyperthermia, anti-hormonal therapy) could significantly enhance tumor sensitivity to anti-cancer immunotherapy. It is important that lower-dose (metronomic) chemotherapy regimens, which are well-tolerated by normal cells, could advance immune-mediated control over tumor growth. EXPERT OPINION We envisage that combined immunotherapy regimens in the context of traditional treatment could become the mainstream modality for treating cancers in all phases of the tumorigenesis. The effectiveness of the anti-cancer treatment could be monitored by the following blood parameters: C-reactive protein, lactate dehydrogenase, and neutrophil-to-lymphocyte ratio.
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Affiliation(s)
- Victor I Seledtsov
- Center for Integral Immunotherapy, Central Clinical Hospital of the Russian Academy of Sciences, Moscow, Russia.,Department of Immunology, Innovita Research Company, Vilnius, Lithuania
| | - Alexei von Delwig
- Department of Immunology, Innovita Research Company, Vilnius, Lithuania
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Choi JH, Lee JH, Choi JW. Applications of Bionano Sensor for Extracellular Vesicles Analysis. MATERIALS (BASEL, SWITZERLAND) 2020; 13:E3677. [PMID: 32825537 PMCID: PMC7503349 DOI: 10.3390/ma13173677] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 08/07/2020] [Accepted: 08/17/2020] [Indexed: 12/13/2022]
Abstract
Recently, extracellular vesicles (EVs) and their contents have been revealed to play crucial roles in the intrinsic intercellular communications and have received extensive attention as next-generation biomarkers for diagnosis of diseases such as cancers. However, due to the structural nature of the EVs, the precise isolation and characterization are extremely challenging. To this end, tremendous efforts have been made to develop bionano sensors for the precise and sensitive characterization of EVs from a complex biologic fluid. In this review, we will provide a detailed discussion of recently developed bionano sensors in which EVs analysis applications were achieved, typically in optical and electrochemical methods. We believe that the topics discussed in this review will be useful to provide a concise guideline in the development of bionano sensors for EVs monitoring in the future. The development of a novel strategy to monitor various bio/chemical materials from EVs will provide promising information to understand cellular activities in a more precise manner and accelerates research on both cancer and cell-based therapy.
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Affiliation(s)
- Jin-Ha Choi
- Department of Chemical and Biomolecular Engineering, Sogang University, Seoul 04107, Korea;
| | - Jin-Ho Lee
- School of Biomedical Convergence Engineering, Pusan National University, Yangsan 50612, Korea
| | - Jeong-Woo Choi
- Department of Chemical and Biomolecular Engineering, Sogang University, Seoul 04107, Korea;
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Nicoliche CYN, de Oliveira RAG, da Silva GS, Ferreira LF, Rodrigues IL, Faria RC, Fazzio A, Carrilho E, de Pontes LG, Schleder GR, Lima RS. Converging Multidimensional Sensor and Machine Learning Toward High-Throughput and Biorecognition Element-Free Multidetermination of Extracellular Vesicle Biomarkers. ACS Sens 2020; 5:1864-1871. [PMID: 32597643 DOI: 10.1021/acssensors.0c00599] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Extracellular vesicles (EVs) are a frontier class of circulating biomarkers for the diagnosis and prognosis of different diseases. These lipid structures afford various biomarkers such as the concentrations of the EVs (CV) themselves and carried proteins (CP). However, simple, high-throughput, and accurate determination of these targets remains a key challenge. Herein, we address the simultaneous monitoring of CV and CP from a single impedance spectrum without using recognizing elements by combining a multidimensional sensor and machine learning models. This multidetermination is essential for diagnostic accuracy because of the heterogeneous composition of EVs and their molecular cargoes both within the tumor itself and among patients. Pencil HB cores acting as electric double-layer capacitors were integrated into a scalable microfluidic device, whereas supervised models provided accurate predictions, even from a small number of training samples. User-friendly measurements were performed with sample-to-answer data processing on a smartphone. This new platform further showed the highest throughput when compared with the techniques described in the literature to quantify EVs biomarkers. Our results shed light on a method with the ability to determine multiple EVs biomarkers in a simple and fast way, providing a promising platform to translate biofluid-based diagnostics into clinical workflows.
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Affiliation(s)
- Caroline Y. N. Nicoliche
- Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, São Paulo 13083-970, Brazil
- Institute of Chemistry, University of Campinas, Campinas, São Paulo 13083-970, Brazil
| | - Ricardo A. G. de Oliveira
- Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, São Paulo 13083-970, Brazil
| | - Giulia S. da Silva
- Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, São Paulo 13083-970, Brazil
- Institute of Chemistry, University of Campinas, Campinas, São Paulo 13083-970, Brazil
| | - Larissa F. Ferreira
- Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, São Paulo 13083-970, Brazil
- Institute of Chemistry, University of Campinas, Campinas, São Paulo 13083-970, Brazil
| | - Ian L. Rodrigues
- Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, São Paulo 13083-970, Brazil
| | - Ronaldo C. Faria
- Department of Chemistry, Federal University of São Carlos, São Carlos, São Paulo 13565-905, Brazil
| | - Adalberto Fazzio
- Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, São Paulo 13083-970, Brazil
- Federal University of ABC, Santo André, São Paulo 09210-580, Brazil
| | - Emanuel Carrilho
- São Carlos Institute of Chemistry, University of São Paulo, São Carlos, São Paulo 13566-590, Brazil
| | - Letícia G. de Pontes
- São Carlos Institute of Chemistry, University of São Paulo, São Carlos, São Paulo 13566-590, Brazil
| | - Gabriel R. Schleder
- Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, São Paulo 13083-970, Brazil
- Federal University of ABC, Santo André, São Paulo 09210-580, Brazil
| | - Renato S. Lima
- Brazilian Nanotechnology National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, São Paulo 13083-970, Brazil
- Institute of Chemistry, University of Campinas, Campinas, São Paulo 13083-970, Brazil
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Xu L, Shoaie N, Jahanpeyma F, Zhao J, Azimzadeh M, Al Jamal KT. Optical, electrochemical and electrical (nano)biosensors for detection of exosomes: A comprehensive overview. Biosens Bioelectron 2020; 161:112222. [PMID: 32365010 DOI: 10.1016/j.bios.2020.112222] [Citation(s) in RCA: 115] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Revised: 04/14/2020] [Accepted: 04/16/2020] [Indexed: 12/13/2022]
Abstract
Exosomes are small extracellular vesicles involved in many physiological activities of cells in the human body. Exosomes from cancer cells have great potential to be applied in clinical diagnosis, early cancer detection and target identification for molecular therapy. While this field is gaining increasing interests from both academia and industry, barriers such as supersensitive detection techniques and highly-efficient isolation methods remain. In the clinical settings, there is an urgent need for rapid analysis, reliable detection and point-of-care testing (POCT). With these challenges to be addressed, this article aims to review recent developments and technical breakthroughs including optical, electrochemical and electrical biosensors for exosomes detection in the field of cancer and other diseases and demonstrate how nanobiosensors could enhance the performance of conventional sensors. Working strategies, limit of detections, advantages and shortcomings of the studies are summarized. New trends, challenges and future perspectives of exosome-driven POCT in liquid biopsy have been discussed.
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Affiliation(s)
- Lizhou Xu
- Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, United Kingdom
| | - Nahid Shoaie
- Department of Biotechnology, Tarbiat Modares University of Medical Science, Tehran, Iran
| | - Fatemeh Jahanpeyma
- Department of Biotechnology, Tarbiat Modares University of Medical Science, Tehran, Iran
| | - Junjie Zhao
- Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, United Kingdom
| | - Mostafa Azimzadeh
- Medical Nanotechnology & Tissue Engineering Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, 89195-999, Yazd, Iran; Stem Cell Biology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, 89195-999, Yazd, Iran; Department of Advanced Medical Sciences and Technologies, School of Paramedicine, Shahid Sadoughi University of Medical Sciences, 8916188635, Yazd, Iran.
| | - Khuloud T Al Jamal
- Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, United Kingdom.
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The function and clinical application of extracellular vesicles in innate immune regulation. Cell Mol Immunol 2020; 17:323-334. [PMID: 32203193 PMCID: PMC7109106 DOI: 10.1038/s41423-020-0391-1] [Citation(s) in RCA: 206] [Impact Index Per Article: 41.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Accepted: 02/17/2020] [Indexed: 12/21/2022] Open
Abstract
The innate immune system plays a crucial role in the host defense against viral and microbial infection. Exosomes constitute a subset of extracellular vesicles (EVs) that can be released by almost all cell types. Owing to their capacity to shield the payload from degradation and to evade recognition and subsequent removal by the immune system, exosomes efficiently transport functional components to recipient cells. Accumulating evidence has recently shown that exosomes derived from tumor cells, host cells and even bacteria and parasites mediate the communication between the invader and innate immune cells and thus play an irreplaceable function in the dissemination of pathogens and donor cell-derived molecules, modulating the innate immune responses of the host. In this review, we describe the current understanding of EVs (mainly focusing on exosomes) and summarize and discuss their crucial roles in determining innate immune responses. Additionally, we discuss the potential of using exosomes as biomarkers and cancer vaccines in diagnostic and therapeutic applications.
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Sierra J, Marrugo-Ramírez J, Rodriguez-Trujillo R, Mir M, Samitier J. Sensor-Integrated Microfluidic Approaches for Liquid Biopsies Applications in Early Detection of Cancer. SENSORS (BASEL, SWITZERLAND) 2020; 20:E1317. [PMID: 32121271 PMCID: PMC7085501 DOI: 10.3390/s20051317] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Revised: 02/21/2020] [Accepted: 02/24/2020] [Indexed: 12/13/2022]
Abstract
Cancer represents one of the conditions with the most causes of death worldwide. Common methods for its diagnosis are based on tissue biopsies-the extraction of tissue from the primary tumor, which is used for its histological analysis. However, this technique represents a risk for the patient, along with being expensive and time-consuming and so it cannot be frequently used to follow the progress of the disease. Liquid biopsy is a new cancer diagnostic alternative, which allows the analysis of the molecular information of the solid tumors via a body fluid draw. This fluid-based diagnostic method displays relevant advantages, including its minimal invasiveness, lower risk, use as often as required, it can be analyzed with the use of microfluidic-based platforms with low consumption of reagent, and it does not require specialized personnel and expensive equipment for the diagnosis. In recent years, the integration of sensors in microfluidics lab-on-a-chip devices was performed for liquid biopsies applications, granting significant advantages in the separation and detection of circulating tumor nucleic acids (ctNAs), circulating tumor cells (CTCs) and exosomes. The improvements in isolation and detection technologies offer increasingly sensitive and selective equipment's, and the integration in microfluidic devices provides a better characterization and analysis of these biomarkers. These fully integrated systems will facilitate the generation of fully automatized platforms at low-cost for compact cancer diagnosis systems at an early stage and for the prediction and prognosis of cancer treatment through the biomarkers for personalized tumor analysis.
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Affiliation(s)
- Jessica Sierra
- Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC) Barcelona Institute of Science and Technology (BIST), 12 Baldiri Reixac 15-21, 08028 Barcelona, Spain; (J.S.); (R.R.-T.); (J.S.)
- Department of Electronics and Biomedical Engineering, University of Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain;
| | - José Marrugo-Ramírez
- Department of Electronics and Biomedical Engineering, University of Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain;
| | - Romen Rodriguez-Trujillo
- Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC) Barcelona Institute of Science and Technology (BIST), 12 Baldiri Reixac 15-21, 08028 Barcelona, Spain; (J.S.); (R.R.-T.); (J.S.)
- Department of Electronics and Biomedical Engineering, University of Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain;
| | - Mònica Mir
- Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC) Barcelona Institute of Science and Technology (BIST), 12 Baldiri Reixac 15-21, 08028 Barcelona, Spain; (J.S.); (R.R.-T.); (J.S.)
- Department of Electronics and Biomedical Engineering, University of Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain;
- Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Monforte de Lemos 3-5, Pabellón 11, 28029 Madrid, Spain
| | - Josep Samitier
- Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC) Barcelona Institute of Science and Technology (BIST), 12 Baldiri Reixac 15-21, 08028 Barcelona, Spain; (J.S.); (R.R.-T.); (J.S.)
- Department of Electronics and Biomedical Engineering, University of Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain;
- Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Monforte de Lemos 3-5, Pabellón 11, 28029 Madrid, Spain
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47
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Mathew DG, Beekman P, Lemay SG, Zuilhof H, Le Gac S, van der Wiel WG. Electrochemical Detection of Tumor-Derived Extracellular Vesicles on Nanointerdigitated Electrodes. NANO LETTERS 2020; 20:820-828. [PMID: 31536360 PMCID: PMC7020140 DOI: 10.1021/acs.nanolett.9b02741] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 09/04/2019] [Indexed: 05/15/2023]
Abstract
Tumor-derived extracellular vesicles (tdEVs) are attracting much attention due to their essential function in intercellular communication and their potential as cancer biomarkers. Although tdEVs are significantly more abundant in blood than other cancer biomarkers, their concentration compared to other blood components remains relatively low. Moreover, the presence of particles in blood with a similar size as that of tdEVs makes their selective and sensitive detection further challenging. Therefore, highly sensitive and specific biosensors are required for unambiguous tdEV detection in complex biological environments, especially for decentralized point-of-care analysis. Here, we report an electrochemical sensing scheme for tdEV detection, with two-level selectivity provided by a sandwich immunoassay and two-level amplification through the combination of an enzymatic assay and redox cycling on nanointerdigitated electrodes to respectively enhance the specificity and sensitivity of the assay. Analysis of prostate cancer cell line tdEV samples at various concentrations revealed an estimated limit of detection for our assay as low as 5 tdEVs/μL, as well as an excellent linear sensor response spreading over 6 orders of magnitude (10-106 tdEVs/μL), which importantly covers the clinically relevant range for tdEV detection in blood. This novel nanosensor and associated sensing scheme opens new opportunities to detect tdEVs at clinically relevant concentrations from a single blood finger prick.
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Affiliation(s)
- Dilu G. Mathew
- NanoElectronics
Group, MESA+ Institute for Nanotechnology, University of Twente, P.O. Box 217, Enschede, 7500 AE The
Netherlands
| | - Pepijn Beekman
- Laboratory
for Organic Chemistry, Wageningen University, Stippeneng 4, Wageningen, 6708WE The
Netherlands
- Applied
Microfluidics for BioEngineering Research, MESA+ Institute for Nanotechnology,
TechMed Center, University of Twente, P.O. Box 217, Enschede, 7500 AE The Netherlands
| | - Serge G. Lemay
- Bioelectronics,
MESA+ Institute for Nanotechnology, University
of Twente, P.O. Box 217, Enschede, 7500 AE The Netherlands
| | - Han Zuilhof
- Laboratory
for Organic Chemistry, Wageningen University, Stippeneng 4, Wageningen, 6708WE The
Netherlands
- School
of Pharmaceutical Sciences and Technology, Tianjin University, Tianjin, 300072 China
- Department
of Chemical and Materials Engineering, King
Abdulaziz University, Jeddah, 21589 Saudi Arabia
| | - Séverine Le Gac
- Applied
Microfluidics for BioEngineering Research, MESA+ Institute for Nanotechnology,
TechMed Center, University of Twente, P.O. Box 217, Enschede, 7500 AE The Netherlands
| | - Wilfred G. van der Wiel
- NanoElectronics
Group, MESA+ Institute for Nanotechnology, University of Twente, P.O. Box 217, Enschede, 7500 AE The
Netherlands
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48
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49
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Xie F, Zhou X, Fang M, Li H, Su P, Tu Y, Zhang L, Zhou F. Extracellular Vesicles in Cancer Immune Microenvironment and Cancer Immunotherapy. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2019; 6:1901779. [PMID: 31871860 PMCID: PMC6918121 DOI: 10.1002/advs.201901779] [Citation(s) in RCA: 207] [Impact Index Per Article: 34.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/13/2019] [Revised: 09/26/2019] [Indexed: 05/10/2023]
Abstract
Extracellular vesicles (EVs) are secreted by almost all cells. They contain proteins, lipids, and nucleic acids which are delivered from the parent cells to the recipient cells. Thereby, they function as mediators of intercellular communication and molecular transfer. Recent evidences suggest that exosomes, a small subset of EVs, are involved in numerous physiological and pathological processes and play essential roles in remodeling the tumor immune microenvironment even before the occurrence and metastasis of cancer. Exosomes derived from tumor cells and host cells mediate their mutual regulation locally or remotely, thereby determining the responsiveness of cancer therapies. As such, tumor-derived circulating exosomes are considered as noninvasive biomarkers for early detection and diagnosis of tumor. Exosome-based therapies are also emerging as cutting-edge and promising strategies that could be applied to suppress tumor progression or enhance anti-tumor immunity. Herein, the current understanding of exosomes and their key roles in modulating immune responses, as well as their potential therapeutic applications are outlined. The limitations of current studies are also presented and directions for future research are described.
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Affiliation(s)
- Feng Xie
- Institute of Biology and Medical ScienceSoochow UniversitySuzhou215123P. R. China
- MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhou310058P. R. China
| | - Xiaoxue Zhou
- MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhou310058P. R. China
- Key Laboratory of Head & Neck CancerTranslational Research of Zhejiang ProvinceZhejiang Cancer HospitalHangzhou310058P. R. China
| | - Meiyu Fang
- Key Laboratory of Head & Neck CancerTranslational Research of Zhejiang ProvinceZhejiang Cancer HospitalHangzhou310058P. R. China
| | - Heyu Li
- MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhou310058P. R. China
| | - Peng Su
- MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhou310058P. R. China
| | - Yifei Tu
- MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhou310058P. R. China
| | - Long Zhang
- MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhou310058P. R. China
| | - Fangfang Zhou
- Institute of Biology and Medical ScienceSoochow UniversitySuzhou215123P. R. China
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50
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Dong Z, Tang C, Zhang Z, Zhou W, Zhao R, Wang L, Xu J, Wu Y, Wu J, Zhang X, Xu L, Zhao L, Fang X. Simultaneous Detection of Exosomal Membrane Protein and RNA by Highly Sensitive Aptamer Assisted Multiplex–PCR. ACS APPLIED BIO MATERIALS 2019; 3:2560-2567. [DOI: 10.1021/acsabm.9b00825] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Zaizai Dong
- Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China
- University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Chuanhao Tang
- Department of Medical Oncology, Peking University International Hospital, Beijing 102206, P. R. China
| | - Zhen Zhang
- Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China
| | - Wei Zhou
- Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China
- University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Rong Zhao
- Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China
- University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Lina Wang
- Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China
- University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Jiachao Xu
- Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China
- University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Yayun Wu
- Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China
- University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Jiang Wu
- University of Chinese Academy of Sciences, Beijing 100049, P. R. China
| | - Xing Zhang
- Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China
| | - Li Xu
- Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China
| | - Libo Zhao
- Echo Biotech Co., Ltd, Beijing 102206, P. R. China
| | - Xiaohong Fang
- Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China
- University of Chinese Academy of Sciences, Beijing 100049, P. R. China
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