Rationally Designed Peptide Probes for Extracellular Vesicles

Tamura, Ryo; Yin, Hang

doi:10.1016/bs.acc.2016.09.001

Cited by 3 publications

(6 citation statements)

References 72 publications

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“…The study shows that the Vn96 based method obtained higher yield than of UC [ 93 ]. Many other peptide aptamers, such as A8 and A17 bind to the different domain of HSP70, peptide aptamer MARCKS-ED and bradykinin (BK) trimer bind to PS [ 94 ], peptide aptamer LXY30 targeted α3β1 integrin has been used to develop exosome isolation technology. All these exosome isolation method might have high potential to isolate specific tumor-derived exosome [ 95 , 96 ].…”

Section: Exosome Enrichment Methodsmentioning

confidence: 99%

Progress in exosome associated tumor markers and their detection methods

Shen

He³

et al. 2020

Mol Biomed

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Exosomes are secreted by cells and are widely present in body fluids. Exosomes contain various molecular constituents of their cells of origin such as proteins, mRNA, miRNAs, DNA, lipid and glycans which are very similar as the content in tumor cells. These contents play an important role in various stages of tumor development, and make the tumor-derived exosome as a hot and emerging biomarker for various cancers diagnosis and management in non-invasive manner. The present problems of exosome isolation and detection hinder the application of exosomes. With the development of exosome isolation and detection technology, the contents of exosomes can be exploited for early cancer diagnosis. This review summarizes the recent progress on exosomeassociated tumor biomarkers and some new technologies for exosome isolation and detection. Furthermore, we have also discussed the future development direction in exosome analysis methods. Development on exosome tumor markers Extracellular vesicle (EV) includes exosomes, microvesicles and apoptotic bodies. These vesicles have different size and biogenesis. Exosomes are complex 20-100 nm vesicles and generate in a way that intracellular multivesicular bodies (MVBs) containing intraluminal vesicles (ILVs) fuse with the plasma membrane [1]. Larger vesicles, microvesicles (100 nm-1 μm) and apoptotic bodies (1-5 μm), are released directly from the budding and fission of the plasma membrane [2]. In the past decades, researchers have become increasingly interested in the role of EVs, especially exosomes, in diseases. Exosomes contain various molecular constituents of their cell of origin such as proteins, RNAs, DNA, lipid glycans. Therefore, tumor-derived exosomes could tell the physiological and pathological states of parent tumor cells, and emerged to be a hot cancer biomarker in liquid biopsy field [3]. Given the rich molecular composition of exosomes and easy availability of liquid biopsy sample, many researchers [4] are pursuing to develop non-invasive diagnostic methods with higher sensitivity and specificity based on exosome, which has very high potential to help early diagnosis, treatment evaluation, and prognostic analysis of the disease. In this section, we have summarized the application of exosomes in tumor diagnosis based on its amount and molecular compositions. Level of exosomes in tumor diagnosis Studies show that the level of exosomes in plasma was significantly higher in cancers (such as ovarian cancer [5] and non-small-cell-lung cancer [6]) patients than that of healthy controls [7]. Therefore, many researchers hypothesize that levels of exosome in bodily fluid can serve as a potential diagnostic biomarker in cancer patients. Logozzi et al. [8] investigated the amount of

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Section: Exosome Enrichment Methodsmentioning

confidence: 99%

Progress in exosome associated tumor markers and their detection methods

Shen

He³

et al. 2020

Mol Biomed

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“…As already discussed by Tamura and Yin, 100 the need to find new peptide probes for EVs -targeting for instance protein domains regulating membrane curvature -might help biosensor scientists to develop new peptide forms for the isolation and detection of EVs. The development of an EV target library might be a useful knowledge base to enhance the research of new specific probes either for isolation or detection.…”

Section: Discussionmentioning

confidence: 99%

“…The challenge of designing efficient peptides for EVs is discussed by Tamura and Yin in their book chapter. 100 EVs display universal protein markers: tetraspanins, Ras superfamily GTPase proteins and Heat Shock Proteins (HSP). In addition, lipids that compose the membranes of EVs are also interesting targets for peptide probe design.…”

Section: Emerging Peptide Probes Dedicated To Evsmentioning

confidence: 99%

“…Based on the fact that EV lipids are enriched with phosphatidylserine, 101 Yin's research group, developed three peptides based on characteristic membrane proteins displayed on EVs. 100 A first peptide probe, based on the intracellular membrane protein Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS), has been developed by Yin's research group. 102 This synthetic peptide called MARCKS-ED selectively binds phosphatidylserine on EV lipid membranes.…”

Section: Emerging Peptide Probes Dedicated To Evsmentioning

confidence: 99%

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Biosensing extracellular vesicles: contribution of biomolecules in affinity-based methods for detection and isolation

Gaillard

Thuaire

Nonglaton

et al. 2020

Analyst

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“…EVs consist of exosomes with diameters of 30–150 nm and microvesicles with diameters of 100–1000 nm. Exosomes are released by exocytosis after being formed in the endosome, and microvesicles are produced by direct budding from the plasma membrane. − EVs have been intensely studied in biomedical research including cancer growth and metastasis, immune system modulation, and drug delivery system development. − Exosomes derived from cancer cells deliver oncogenic molecules to tumor microenvironments and sites of future metastases. For instance, exosomes from cancer cells prepare the environment for incoming cancer cells in premetastatic sites. , Furthermore, cancer cell-derived exosomes transfer signaling molecules to the immune system that modulate the immune response against cancer cells. ,, Exosomes have been used for delivering therapeutic cargo such as small molecules, proteins, and nucleic acids to disease sites in preclinical and clinical studies. ,,− …”

Section: Introductionmentioning

confidence: 99%

Photoactivatable Prodrug of Doxazolidine Targeting Exosomes

Tamura

Balabanova²,

Frakes³

et al. 2019

J. Med. Chem.

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Natural lipid nanocarriers, exosomes, carry cell-signaling materials such as DNA and RNA for intercellular communications. Exosomes derived from cancer cells contribute to the progression and metastasis of cancer cells by transferring oncogenic signaling molecules to neighboring and remote premetastatic sites. Therefore, applying the unique properties of exosomes for cancer therapy has been expected in science, medicine, and drug discovery fields. Herein, we report that an exosome-targeting prodrug system, designated MARCKS−ED−photodoxaz, could spatiotemporally control the activation of an exquisitely cytotoxic agent, doxazolidine (doxaz), with UV light. The MARCKS−ED peptide enters a cell by forming a complex with the exosomes in situ at its plasma membrane and in the media. MARCKS−ED− photodoxaz releases doxaz under near-UV irradiation to inhibit cell growth with low nanomolar IC 50 values. The MARCKS−ED−photodoxaz system targeting exosomes and utilizing photochemistry will potentially provide a new approach for the treatment of cancer, especially for highly progressive and invasive metastatic cancers.

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Rationally Designed Peptide Probes for Extracellular Vesicles

Cited by 3 publications

References 72 publications

Progress in exosome associated tumor markers and their detection methods

Progress in exosome associated tumor markers and their detection methods

Biosensing extracellular vesicles: contribution of biomolecules in affinity-based methods for detection and isolation

Photoactivatable Prodrug of Doxazolidine Targeting Exosomes

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