Microfluidic platforms for extracellular vesicle isolation, analysis and therapy in cancer

Abreu, Catarina M.; Costa-Silva, Bruno; Reis, Rui L.; Kundu, Subhas C.; Caballero, David

doi:10.1039/d2lc00006g

Cited by 31 publications

(24 citation statements)

References 133 publications

(156 reference statements)

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“…However, the concentration of EVs with good potential to be disease markers in biological samples could be very low, making it very challenging to detect such EVs using conventional methods like ELISA, western blotting (WB), and flow cytometry (FCM) . State-of-the-art sensors built on microfluidic and nanofluidic devices have been developed to detect EVs down to 100 particles/mL. ,− Still, simple but sensitive techniques for rapid EV detection are in demand to speed up the discovery and clinical applications of EV-based disease markers.…”

Section: Introductionmentioning

confidence: 99%

Bimetallic Metal–Organic Framework Fe/Co-MIL-88(NH₂) Exhibiting High Peroxidase-like Activity and Its Application in Detection of Extracellular Vesicles

Jiang

Xiao

Hong

et al. 2022

ACS Appl. Mater. Interfaces

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Metal–organic frameworks (MOFs) have many attractive features, including tunable composition, rigid structure, controllable pore size, and large specific surface area, and thus are highly applicable in molecular analysis. Depending on the MOF structure, a high number of unsaturated metal sites can be exposed to catalyze chemical reactions. In the present work, we report that using both Co(II) and Fe(III) to prepare the MIL-88(NH2) MOF, we can produce the bimetallic MOF that can catalyze the conversion of 3,3′,5,5″-tetramethylbenzidine (TMB) to a color product through a reaction with H2O2 at a higher reaction rate than the monometallic Fe-MIL-88(NH2). The Michaelis constants (K m) of the catalytic reaction for TMB and H2O2 are 3–5 times smaller, and the catalytic constants (k cat) are 5–10 times higher than those of the horseradish peroxidase (HRP), supporting ultrahigh peroxidase-like activity. These values are also much more superior to those of the HRP-mimicking MOFs reported previously. Interestingly, the bimetallic MOF can be coupled with glucose oxidase (GOx) to trigger the cascade enzymatic reaction for highly sensitive detection of extracellular vesicles (EVs), a family of important biomarkers. Through conjugation to the aptamer that recognizes the marker protein on EV surface, the MOF can help isolate the EVs from biological matrices, which are subsequently labeled by GOx via antibody recognition. The cascade enzymatic reaction between MOF and GOx enables the detection of EVs at a concentration as low as 7.8 × 104 particles/mL. The assay can be applied to monitor EV secretion by cultured cells and also can successfully detect the different EV quantities in the sera samples collected from cancer patients and healthy controls. Overall, we prove that the bimetallic Fe/Co-MIL-88(NH2) MOF, with its high peroxidase activity and high biocompatibility, is a valuable tool deployable in clinical assays to facilitate disease diagnosis and prognosis.

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Section: Introductionmentioning

confidence: 99%

Bimetallic Metal–Organic Framework Fe/Co-MIL-88(NH₂) Exhibiting High Peroxidase-like Activity and Its Application in Detection of Extracellular Vesicles

Jiang

Xiao

Hong

et al. 2022

ACS Appl. Mater. Interfaces

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“…[99][100][101][102] In addition, microfluidics offered efficient EV isolation candidate for fast diagnostic and analysis, but low yield might limit the further application of EVs. [84,87,103] Besides, precipitation method also provided possibility for efficient EV isolation. [88,89] The hydrophilic polymers, like poly(ethylene glycol) (PEG), could competitively bind with free water molecules surrounding EVs to create hydrophobic environment, resulting in the precipitation of EVs with relatively high yield.…”

Section: Preparation Of Ev-based Drug Delivery Systemsmentioning

confidence: 99%

Extracellular‐Vesicle‐Based Drug Delivery Systems for Enhanced Antitumor Therapies through Modulating the Cancer‐Immunity Cycle

et al. 2022

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Although immunotherapy harnessing activity of the immune system against tumors has made great progress, the treatment efficacy remains limited in most cancers. Current anticancer immunotherapy is primarily based on T‐cell‐mediated cellular immunity, which highly relies on efficiency of triggering the cancer‐immunity cycle, namely, tumor antigen release, antigen presentation by antigen presenting cells, T cell activation, recruitment and infiltration of T cells into tumors, and recognition and killing of tumor cells by T cells. Unfortunately, these immunotherapies are restricted by inefficient drug delivery and acting on only a single step of the cancer‐immunity cycle. Due to high biocompatibility, low immunogenicity, intrinsic cell targeting, and easy chemical and genetic manipulation, extracellular vesicle (EV)‐based drug delivery systems are widely used to amplify anticancer immune responses by serving as an integrated platform for multiple drugs or therapeutic strategies to synergistically activate several steps of cancer‐immunity cycle. This review summarizes various mechanisms related to affecting cancer‐immunity cycle disorders. Meanwhile, preparation and application of EV‐based drug delivery systems in modulating cancer‐immunity cycle are introduced, especially in the improvement of T cell recruitment and infiltration into tumors. Finally, opportunities and challenges of EV‐based drug delivery systems in translational clinical applications are briefly discussed.

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“…Therefore researchers have recently started integrating different methods based on the physical properties of exosomes with the design of the microfluidic device. Thus, microfluidics-based isolation techniques have developed and evolved over the years [ 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. The following sections will discuss some of the most interesting methods mostly based on the immunoaffinity approaches.…”

Section: Isolation and Detection Techniquesmentioning

confidence: 99%

Microfluidic Platforms for the Isolation and Detection of Exosomes: A Brief Review

et al. 2022

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Extracellular vesicles (EVs) are a group of communication organelles enclosed by a phospholipid bilayer, secreted by all types of cells. The size of these vesicles ranges from 30 to 1000 nm, and they contain a myriad of compounds such as RNA, DNA, proteins, and lipids from their origin cells, offering a good source of biomarkers. Exosomes (30 to 100 nm) are a subset of EVs, and their importance in future medicine is beyond any doubt. However, the lack of efficient isolation and detection techniques hinders their practical applications as biomarkers. Versatile and cutting-edge platforms are required to detect and isolate exosomes selectively for further clinical analysis. This review paper focuses on lab-on-chip devices for capturing, detecting, and isolating extracellular vesicles. The first part of the paper discusses the main characteristics of different cell-derived vesicles, EV functions, and their clinical applications. In the second part, various microfluidic platforms suitable for the isolation and detection of exosomes are described, and their performance in terms of yield, sensitivity, and time of analysis is discussed.

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Microfluidic platforms for extracellular vesicle isolation, analysis and therapy in cancer

Abstract: Extracellular vesicles (EVs) are small lipidic particles packed with proteins, DNA, messenger RNA and microRNAs of their cell of origin that act as critical players in cell-cell communication. These vesicles...

Cited by 31 publications

References 133 publications

Bimetallic Metal–Organic Framework Fe/Co-MIL-88(NH₂) Exhibiting High Peroxidase-like Activity and Its Application in Detection of Extracellular Vesicles

Bimetallic Metal–Organic Framework Fe/Co-MIL-88(NH₂) Exhibiting High Peroxidase-like Activity and Its Application in Detection of Extracellular Vesicles

Extracellular‐Vesicle‐Based Drug Delivery Systems for Enhanced Antitumor Therapies through Modulating the Cancer‐Immunity Cycle

Microfluidic Platforms for the Isolation and Detection of Exosomes: A Brief Review

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Microfluidic platforms for extracellular vesicle isolation, analysis and therapy in cancer

Abstract: Extracellular vesicles (EVs) are small lipidic particles packed with proteins, DNA, messenger RNA and microRNAs of their cell of origin that act as critical players in cell-cell communication. These vesicles...

Cited by 31 publications

References 133 publications

Bimetallic Metal–Organic Framework Fe/Co-MIL-88(NH2) Exhibiting High Peroxidase-like Activity and Its Application in Detection of Extracellular Vesicles

Bimetallic Metal–Organic Framework Fe/Co-MIL-88(NH2) Exhibiting High Peroxidase-like Activity and Its Application in Detection of Extracellular Vesicles

Extracellular‐Vesicle‐Based Drug Delivery Systems for Enhanced Antitumor Therapies through Modulating the Cancer‐Immunity Cycle

Microfluidic Platforms for the Isolation and Detection of Exosomes: A Brief Review

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Product

Resources

About

Bimetallic Metal–Organic Framework Fe/Co-MIL-88(NH₂) Exhibiting High Peroxidase-like Activity and Its Application in Detection of Extracellular Vesicles

Bimetallic Metal–Organic Framework Fe/Co-MIL-88(NH₂) Exhibiting High Peroxidase-like Activity and Its Application in Detection of Extracellular Vesicles