Exosomes Barcoding: A smart approach for cancer liquid biopsy

Abstract

Cancer is an unsolved health crisis worldwide. Extracellular vesicles (EVs) address this problem in a new way. In cancer, early detection is highly challenging, exosomes (a subpopulation of EVs, originating from endosomes) overcomes this limitation. In cancer, tumor-derived exosomes (TEXs) play a role as signaling molecules in cancer development and progression. TEXs provide detailed investigation for specific cancer biomarkers research. Exosomes heterogeneity (variation in exosomes size, exosomes origin, and inner molecular diversity) has led to complications in understanding and studying cancer liquid biopsies. Single exosome profiling and exosomes barcoding has helped in supporting and overcoming this limitation and has played a significant role in precision oncology. Exosomes barcoding is a promising interdisciplinary approach for screening cancers more specifically.

Keywords: Biomarkers; Cancer; Exosomes; Exosomes barcoding; Sensor.

Fig. 1

Exosomes Barcoding approaches. Physical Methods (Electrochemical Detection. a.1. CD63 antibody-coated magnetic beads capture EVs conjugated with HRP enzyme, a.2. Image of Integrated Magnetic Electrochemical exosomes sensor (iMEXs), a.3. Internal structure of iMEXs, a.4. Detection comparison between iMEXs and ELISA using human plasma samples, a.5. Ovarian cancer patient's EpCAM and CD24 levels analysis via iMEXs. (Reproduced with permission from Ref. 2 Copyright 2018 American Chemical Society), Chemical Methods (Fluorescence dye-based exosomes tracking method, b.1. Photograph of Fluorescence tag-based exosomes separation via microfluidic method, b.2. Plot of flow rate, b.3. Exosomes capture rate in mixed flow with purity, b.4 Fluorescence tag-based ovarian cancer plasma sample exosomes separation with different dilutions, b.5. Fluorescence tag using three separate colours, ovarian tumor marker expression analysis via ExoSearch chip method (Reproduced with permission under Creative Commons CC BY 3.0 license from Ref. 9 Copyright 2016 Royal Society of Chemistry) Nanomaterial-based method (nanomaterial surface plasma resonance-based approach) c.1. Whole image of gold film of Nano-plasmonic Exosomes (nPLEXs) Sensor, c.2. Photograph of the electromagnetic field of nanohole surface and the capture EVs, c.3. Multichannel Microfluidic Chamber. c.4. Transmission Spectra of EVs detection, c.5. nPLEX method compared to ELISA and Western blotting, c.6. nPLEX and ELISA-based comparative analysis of protein expression. (Reproduced with permission from Ref. 2 Copyright 2018 American Chemical Society), Biological Methods (Antibody and DNA conjugated based exosomes screening) d.1 Proximity-dependent Barcoding Assay (PBA) , d.2. Preparation of rolling circle amplification (RCA) products, d.3. Exosomes surface protein profiling via PBA (Reproduced with permission under Creative Commons CC BY 4.0 license from Ref. 7 Copyright 2019 The Authors.). (For color images the readers can refer to the online version of this article.)

Fig. 2

Single exosome profiling (Reproduced with permission from ref. 27 Copyright 2022 American Chemical Society).