Engineered nanointerfaces for microfluidic isolation and molecular profiling of tumor-specific extracellular vesicles

Reátegui, Eduardo; Vos, Kristan E. van der; Lai, Charles P.; Zeinali, Mahnaz; Atai, Nadia A.; Aldikacti, Berent; Floyd, Frederick P.; Khankhel, Aimal H.; Thapar, Vishal; Hochberg, Fred H.; Sequist, Lecia V.; Nahed, Brian V.; Carter, Bob S.; Toner, Mehmet; Balaj, Leonora; Ting, David T.; Breakefield, Xandra O.; Stott, Shannon L.

doi:10.1038/s41467-017-02261-1

Cited by 258 publications

(244 citation statements)

References 58 publications

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“…22, 110–113 In this approach, EVs are captured with specific antibodies against common EV markers including the tetraspanins ( e.g. , CD9, CD63, CD81) as well as tumor-associated markers ( e.g.…”

Section: Ev Enrichmentmentioning

confidence: 99%

New Technologies for Analysis of Extracellular Vesicles

et al. 2018

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Extracellular vesicles (EVs) are diverse, nanoscale membrane vesicles actively released by cells. Similar sized vesicles can be further classified (e.g., exosomes, microvesicles) based on their biogenesis, size and biophysical properties. Although initially thought to be cellular debris, and thus under-appreciated, EVs are now increasingly recognized as important vehicles of intercellular communication and circulating biomarkers for disease diagnoses and prognosis. Despite their clinical potential, the lack of sensitive preparatory and analytical technologies for EVs poses a barrier to clinical translation. New analytical platforms including molecular ones are thus actively being developed to address these challenges. Recent advances in the field are expected to have far-reaching impact in both basic and translational studies. This article aims to present a comprehensive and critical overview of emerging analytical technologies for EV detection, and their clinical applications.

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Section: Ev Enrichmentmentioning

confidence: 99%

New Technologies for Analysis of Extracellular Vesicles

et al. 2018

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“…Microfluidic chip is capable to effectively isolate exosomal ingredients as well. Reategui et al . established a microfluidic platform named (EV)HB‐Chip which captured glioblastoma multiforme‐derived characteristic exosomal RNA within 3 hr, contributing to identifying specific genes and subtypes of this disease.…”

Section: The Innovative Approaches To Detect Tumor‐derived Exosomes Fmentioning

confidence: 99%

The cancer exosomes: Clinical implications, applications and challenges

Tang

Hou

et al. 2019

Intl Journal of Cancer

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The exosome is a small functional vesicle enriched in selected proteins, lipids and nucleic acids, displaying distinct molecular heterogeneity. Exosomes released can transform the extracellular matrix microenvironments, transmit signals and molecules to recipient cells and trigger changes in their pathophysiological functions. Tumor‐derived exosomes mediate the interactions of tumor cells and microenvironment significantly, and they stimulate tumor growth and development through specific signaling pathways related to metastasis, therapeutic resistance and immunosuppression. Exosome biogenesis from tumors often represents abundant biological information, and novel and efficient isolation and detection methods of exosomes provide a promising approach for tumor diagnosis and prognosis estimation. Moreover, exosome can even be developed as therapeutic agents for multiple disease models based on effective material transport characteristics and biofilm specificity. This review reports the clinical implications and challenges of exosomes in cancer progression, therapy resistance, metastasis and immune escape, and underlying cancerogenic pathological phenotypes including fibrosis and viral infection.

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“…Recent IV‐MPM studies have provided preliminary data on EV dynamics and EV effects (see Section ), but the full composition of EVs is unknown. A recent microfluidic platform designed to isolate tumor‐derived EVs from blood was used to provide patient‐derived EVs for next‐generation RNA sequencing, demonstrating the heterogeneity of glioblastomas . A similar approach may be used in the future to provide detailed functional analysis of tumor EVs imaged by IV‐MPM.…”

Section: Extending and Complementing The Capabilities Of Iv‐mpmmentioning

confidence: 99%

Frontiers in intravital multiphoton microscopy of cancer

2019

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Background Cancer is a highly complex disease, which involves the cooperation of tumor cells with multiple types of host cells and the extracellular matrix. Cancer studies that rely solely on static measurements of individual cell types are insufficient to dissect this complexity. In the last two decades, intravital microscopy has established itself as a powerful technique that can significantly improve our understanding of cancer by revealing the dynamic interactions governing cancer initiation, progression, and treatment effects in living animals. This review focuses on intravital multiphoton microscopy (IV‐MPM) applications in mouse models of cancer. Recent findings IV‐MPM studies have already enabled a deeper understanding of the complex events occurring in cancer at the molecular, cellular, and tissue levels. Multiple cell types present in different tissues influence cancer cell behavior via activation of distinct signaling pathways. As a result, the boundaries in the field of IV‐MPM are continuously being pushed to provide an integrated comprehension of cancer. We propose that optics, informatics, and cancer (cell) biology are coevolving as a new field. We have identified four emerging themes in this new field. First, new microscopy systems and image processing algorithms are enabling the simultaneous identification of multiple interactions between the tumor cells and the components of the tumor microenvironment. Second, techniques from molecular biology are being exploited to visualize subcellular structures and protein activities within individual cells of interest and relate those to phenotypic decisions, opening the door for “in vivo cell biology”. Third, combining IV‐MPM with additional imaging modalities or omics studies holds promise for linking the cell phenotype to its genotype, metabolic state, or tissue location. Finally, the clinical use of IV‐MPM for analyzing efficacy of anticancer treatments is steadily growing, suggesting a future role of IV‐MPM for personalized medicine. Conclusion IV‐MPM has revolutionized visualization of tumor‐microenvironment interactions in real time. Moving forward, incorporation of novel optics, automated image processing, and omics technologies in the study of cancer biology, will not only advance our understanding of the underlying complexities but will also leverage the unique aspects of IV‐MPM for clinical use.

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Engineered nanointerfaces for microfluidic isolation and molecular profiling of tumor-specific extracellular vesicles

Cited by 258 publications

References 58 publications

New Technologies for Analysis of Extracellular Vesicles

New Technologies for Analysis of Extracellular Vesicles

The cancer exosomes: Clinical implications, applications and challenges

Frontiers in intravital multiphoton microscopy of cancer

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