Abstract

Exosomes are abundantly secreted by most cells that carry membrane and cytosolic factors that can reflect the physiologic state of their source cells and thus have strong potential to serve as biomarkers for early diagnosis, disease staging, and treatment monitoring. However, traditional diagnostic or prognostic applications that might use exosomes are hindered by the lack of rapid and sensitive assays that can exploit their biological information. An array of assay approaches have been developed to address this deficit, including those that integrate immunoassays with nanoplasmonic sensors to measure changes in optical refractive indexes in response to the binding of low concentrations of their targeted molecules. These sensors take advantage of enhanced and tunable interactions between the electron clouds of nanoplasmonic particles and structures and incident electromagnetic radiation to enable isolation-free and ultrasensitive quantification of disease-associated exosome biomarkers present in complex biological samples. These unique advantages make nanoplasmonic sensing one of the most competitive approaches available for clinical applications and point-of-care tests that evaluate exosome-based biomarkers. This review will briefly summarize the origin and clinical utility of exosomes and the limitations of current isolation and analysis approaches before reviewing the specific advantages and limitations of nanoplasmonic sensing devices and indicating what additional developments are necessary to allow the translation of these approaches into clinical applications.

Highlights

  • Exosomes are abundantly secreted by most cells that carry membrane and cytosolic factors that can reflect the physiologic state of their source cells and have strong potential to serve as biomarkers for early diagnosis, disease staging, and treatment monitoring

  • Mechanisms governing exosome biogenesis are covered in other reviews, but broadly speaking, the secretion and uptake dynamics of exosomes are largely regulated by their membrane proteins, whereas their biological functions depend upon both their surface and internal composition, and all of these are controlled by mechanisms and stimuli that are active during their biogenesis to control their composition.[11,12]

  • Exosome biogenesis begins with inward budding of the plasma membrane to form early endosomes that incorporate plasma membrane proteins,[13,14] which can undergo inward budding events that result in the accumulation of intraluminal vesicles (ILVs) to produce multivesicular bodies (MVBs).[15,16]

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Summary

■ CONCLUSIONS AND FUTURE CHALLENGES

As one of the major subtypes of EVs, exosomes are unique, encapsulated biomolecules that are abundantly secreted by all cells and carry crucial biological information from their cell of origin. Many distinct types of plasmonic metamaterials are readily functionalized with molecules that exhibit affinity to target biomarkers and be employed as biosensors in multiple different applications The specificity of such biosensors can be facilely modified by altering the specificity of their conjugated affinity molecules, such that specific antibodies can be employed to recognize EV biomarkers associated with particular diseases or disease stages to permit disease diagnosis, staging, and treatment monitoring. For such plasmonic biosensors to have clinical utility, they must satisfy several essential requirements. Nanoplasmonic sensing and detection approaches remain a strong potential approach for future clinical applications due to (1) the versatility of plasmonic materials that can be designed, fabricated, and tailored to work at a range of biological wavelengths; (2) the promise they show for reaching ultralow limits of detection; (3) their potential for developing compact, portable, siliconbased devices; and (4) their potential in developing purification-free, automated exosome assays that can reduce variability and operator bias

Special Issue Paper
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