The Potential for Extracellular Vesicles in Nanomedicine: A Review of Recent Advancements and Challenges Ahead

Abstract

Extracellular vesicles (EVs) have emerged as promising tools in diagnostics and therapy for chronic diseases, including cancer and Alzheimer's. Small EVs, also called exosomes, are lipid-bound particles (≈30-150 nm) that play a role in healthy and pathophysiological interactions, including intercellular communication, by transporting bioactive molecules, including proteins, lipids, and nucleic acids. Their ability to cross biological barriers, such as the blood-brain barrier, makes them ideal candidates for targeted therapeutic interventions. In the context of chronic diseases, exosomes can be engineered to deliver active agents, including small molecules and siRNAs to specific target cells, providing a novel approach to precision medicine. Moreover, exosomes show great promise as repositories for diagnostic biomarkers. Their cargo can reflect the physiological and pathological status of the parent cells, making them valuable indicators of disease progression and response to treatment. This paper presents a comprehensive review of the application of exosomes in four chronic diseases: cancer, cardiovascular disease, neurodegenerative disease, and orthopedic disease, which significantly impact global public health due to their high prevalence and associated morbidity and mortality rates. Furthermore, the potential of exosomes as valuable tools for theranostics and disease management is highlighted. Finally, the challenges associated with exosomes and their demonstrated potential for advancing future nanomedicine applications are discussed.

Keywords: biological nanoparticles; biomarkers; chronic diseases; diagnosis; exosomes; therapy.

Figure 1

The different types of EVs, their markers and exosome biogenesis. A schematic illustration of the various types of EVs released by the cells including exosomes, ectosomes, and apoptotic bodies, into the extracellular environment. Exosomes are discharged from cells through a process called exocytosis, whereas ectosomes are released by cells through outward budding of the plasma membrane. Apoptotic bodies help clear cellular debris in late apoptosis. Exosome biogenesis begins with the invagination of the cell membrane to form the early endosome which then transforms into the late endosomes and finally forms the MVB containing intraluminal vesicles which mature into exosomes (created using Biorender.com).

Figure 2

Schematic of diverse functions of exosomes in theranostics of chronic diseases (created using Biorender.com).

Figure 3

The timeline and corresponding distribution of research papers, patents, and clinical applications related to the utilization of synthetic nanomaterials for drug delivery. Reproduced with permission,^{[ 40 ]} 2020 American Chemical Society.

Figure 4

A) Assessing the miR‐144‐3p expression in mice heart tissues using qRT‐PCR; n = 3 per group. B) Representative photos of heart sections using TTC‐stain and quantified data quantifying the size of myocardial infarction one week after MI in mice injected with CTP‐EVs, CTP‐EVs‐CurNC, CTP‐EVs‐CurmiR‐144‐3p, or CTP‐EVs‐Curanti‐miR‐144‐3p; n = 5 per group. C) Representative blots and quantified data showing protein expression in the indicated groups. D,E) Representative M‐mode images (E) and quantified data showing mice injected with CTP‐EVs‐Cur miR‐144‐3p have higher EF% and FS% compared to CTP‐EVs‐Cur anti‐miR‐144‐3p‐injected mice Reproduced with permission,^{[ 91 ]} 2021 Elsevier.

Figure 5

A) MRI of the rat tails in different groups. B) The scores of MRI in different groups. A,B) Show that the MRI score of the MSC‐exosome group was significantly lower compared to the non‐injection group.^{[ 105 ]} C) ALP staining for cell activity (scale bar = 50 µm) shows that ALP staining is stronger in osteoblasts co‐cultured with Exo‐miR‐935 compared to the one co‐cultured with Exo‐miR‐935 inhibitor. D) Detection of calcified nodules by alizarin red staining shows that osteoblasts co‐cultured with Exo‐miR‐935 mimic treatment enhance the deposition of minerals. Reproduced with permission,^{[ 106 ]} 2021 Elsevier.

Figure 6

The potential of exosomal biomarkers for different chronic diseases (created using Biorender.com). Reproduced with permission,^{[ 134 ]} 2022 Authors. Reproduced under the terms of the CC‐BY license.^{[ 9} , ^{135 ]} copyrights 2019 and 2021.