An Immuno-Biochip Selectively Captures Tumor-Derived Exosomes and Detects Exosomal RNAs for Cancer Diagnosis

Yang, Yunchen; Kannisto, Eric; Yu, Guan; Reid, Mary E.; Patnaik, Santosh K.; Wu, Yun

doi:10.1021/acsami.8b13971

Cited by 93 publications

(97 citation statements)

References 56 publications

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“…However, these technologies are not able to separate exosomal microRNAs derived from tumor cells from those released by normal cells, and thus may have limited diagnostic sensitivity. We have developed an immuno-biochip that uses antibodies to capture exosomes expressing tumor-associated proteins to improve the separation of cancer cell-derived exosomes from normal cell-derived exosomes (Yang et al, 2018). However, the immuno-biochip only measures the expression of microRNAs in a subpopulation of exosomes, i.e., exosomes carrying tumor-associated proteins, and cannot measure the levels of microRNAs from all tumor cell-derived exosomes.…”

Section: Discussionmentioning

confidence: 99%

Non-invasive Detection of Exosomal MicroRNAs via Tethered Cationic Lipoplex Nanoparticles (tCLN) Biochip for Lung Cancer Early Detection

Liu

Kannisto

et al. 2020

Front. Genet.

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Circulating microRNAs carried by exosomes have emerged as promising diagnostic biomarkers for cancer because of their abundant amount and remarkable stability in body fluids. Exosomal microRNAs in blood are typically quantified using the RNA isolation-qRT-PCR workflow, which cannot distinguish circulating microRNAs secreted by cancer cells from those released by non-tumor cells, making it potentially less sensitive in detecting cancer-specific microRNA biomarkers. We have developed a sensitive and simple tethered cationic lipoplex nanoparticles (tCLN) biochip to detect exosomal microRNAs in human sera. The tCLN biochip allows the discrimination of tumor-derived exosomes from their non-tumor counterparts, and thus achieves higher detection sensitivity and specificity than qRT-PCR. We have demonstrated the clinical utility of the tCLN biochip in lung cancer diagnosis using sera from normal controls, therapy-naive early stage and late stage non-small cell lung cancer (NSCLC) patients. Total five microRNAs (miR-21, miR-25, miR-155, miR-210, and miR-486) were selected as the biomarkers. Each microRNA biomarker measured by tCLN assay showed higher sensitivity and specificity in lung cancer detection than that measured by qRT-PCR. When all five microRNAs were combined, the tCLN assay distinguished normal controls from all NSCLC patients with sensitivity of 0.969, specificity of 0.933 and AUC of 0.970, and provided much better diagnostic accuracy than qRT-PCR (sensitivity = 0.469, specificity = 1.000, AUC = 0.791). Remarkably, the tCLN assay achieved absolute sensitivity and specificity in discriminating early stage NSCLC patients from normal controls, demonstrating its great potential as a liquid biopsy assay for lung cancer early detection.

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Section: Discussionmentioning

confidence: 99%

Non-invasive Detection of Exosomal MicroRNAs via Tethered Cationic Lipoplex Nanoparticles (tCLN) Biochip for Lung Cancer Early Detection

Liu

Kannisto

et al. 2020

Front. Genet.

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“…Taking advantage of this technique, Yang et al designed a chip to selectively capture lung cancer tumor exosomes from human serum for further measure miR-21 and TTF-1 expression. ( Figure 6B) [90]. By functionalizing an Au coated slide with antibodies against tumor-associated proteins (EGFR and PD-L1), absolute specificity was conquered, separating cancer exosomes from the others.…”

Section: Total Internal Reflection Fluorescence Microscopy (Tirf)mentioning

confidence: 99%

“…(B) miR21 are effectively captured from serum sample of lung cancer patients and detected through TIRF microscopy. Adapted with permission from[90]. Copyright American Chemical Society 2019.…”

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confidence: 99%

Cancer Diagnosis through SERS and Other Related Techniques

Blanco-Formoso

Alvarez-Puebla

2020

IJMS

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Cancer heterogeneity increasingly requires ultrasensitive techniques that allow early diagnosis for personalized treatment. In addition, they should preferably be non-invasive tools that do not damage surrounding tissues or contribute to body toxicity. In this context, liquid biopsy of biological samples such as urine, blood, or saliva represents an ideal approximation of what is happening in real time in the affected tissues. Plasmonic nanoparticles are emerging as an alternative or complement to current diagnostic techniques, being able to detect and quantify novel biomarkers such as specific peptides and proteins, microRNA, circulating tumor DNA and cells, and exosomes. Here, we review the latest ideas focusing on the use of plasmonic nanoparticles in coded and label-free surface-enhanced Raman scattering (SERS) spectroscopy. Moreover, surface plasmon resonance (SPR) spectroscopy, colorimetric assays, dynamic light scattering (DLS) spectroscopy, mass spectrometry or total internal reflection fluorescence (TIRF) microscopy among others are briefly examined in order to highlight the potential and versatility of plasmonics.

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“…Thus, it is imperative to develop novel, facile approaches to achieving simultaneous isolation and analysis for rapid diagnosis. Recently, numerous chip‐based analytic equipment have been fabricated for diagnostic applications, such as the microfluidic‐chip and immuno‐biochip . As a typical paradigm, Shao et al developed a microfluidic platform integrated in immunomagnetic selection, RNA collection and real‐time PCR functionalities to rapid detect exosomal mRNA for glioblastoma diagnosis ( Figure 10 ).…”

Section: Cancer Therapeutic and Diagnostic Applications Of Exosomesmentioning

confidence: 99%

Exosomes: The Indispensable Messenger in Tumor Pathogenesis and the Rising Star in Antitumor Applications

Wang

Wei

et al. 2019

Adv. Biosys.

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understanding of the underlying interaction mechanisms between tumor cells and the TME, as well as derivative tumor treatment strategies, is of great significance for oncology and diagnostic development.Exosomes represent a kind of nanosized (30-150 nm) lipid bilayer membrane vesicles that are naturally secreted by almost all types of cells and exist widely in various body fluids, such as plasma, [4] saliva, [5] perspiration, urine, [6] latex, cerebrospinal fluid, nasal mucus, and ascites. After their discovery in 1983, exosomes were widely considered as useless "cellular waste" for a long time. [7] In 1996, Raposo et. al. [8] demonstrated that exosomes derived from human and murine B lymphocytes could transfer antigen and induce antigen-specific T cell responses, which discovery changed the "cellular waste concept" of exosomes. Renewed interest in exosomes followed recent reports demonstrating that exosomes contribute to various aspects of cellular homeostasis, physiology and pathobiology. [9] Intercellular communication is considered as one of the most fascinating roles of exosomes. [10] As the intercellular vehicles to transport message, exosomes inherit various molecular information (including proteins, nucleic acids, lipids) from the origin cell and reflect the phenotypic state. Moreover, these biological entities subsequently affect physiological and pathological processes such as inflammation, immune surveillance, tumorigenesis. [11] As important parts of the tumor microenvironment (TME), exosomes have been widely investigated in past decades and demonstrated to possess specialized functions in tumor initiation, progression, metastasis, angiogenesis, and drug resistance. [12,13] Moreover, the specific molecular signature inherited from the origin tumor cell endow tumor-derived exosomes with the capacity to predict tumor progression and prognosis. [14,15] On the other hand, immune cell-derived exosomes, such as DC-derived exosomes, NK-derived exosomes and M1 macrophage-derived exosomes, play vital roles in activating antitumor immune response, which properties endow these exosomes with promising potential in acting as tumor therapeutic vaccine. In addition, the vesicular biocompatibility, nanometer dimension size and biochemical properties make sophisticated exosomes a novel promising therapeutic nanoplatform in cancer. [16] In this review, efforts are made to provide a comprehensive and critical overview about recent advances in exosome-related research field, ranging from their biogenesis, secretion, isolation and biological function in tumor pathogenesis to their extensive antitumor applications.As natural secreted nanovesicles through the endolysosomal pathway, exosomes have attracted increasing attention over the past decades. An overwhelming number of studies have provided evidence for the intriguing roles that exosomes play in intercellular communication. They are widely involved in the transmission of biomolecule cargos between original cells and neighboring/distant cells in normal physiologica...

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An Immuno-Biochip Selectively Captures Tumor-Derived Exosomes and Detects Exosomal RNAs for Cancer Diagnosis

Cited by 93 publications

References 56 publications

Non-invasive Detection of Exosomal MicroRNAs via Tethered Cationic Lipoplex Nanoparticles (tCLN) Biochip for Lung Cancer Early Detection

Non-invasive Detection of Exosomal MicroRNAs via Tethered Cationic Lipoplex Nanoparticles (tCLN) Biochip for Lung Cancer Early Detection

Cancer Diagnosis through SERS and Other Related Techniques

Exosomes: The Indispensable Messenger in Tumor Pathogenesis and the Rising Star in Antitumor Applications

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