The therapeutic triad of extracellular vesicles: As drug targets, as drugs, and as drug carriers

Moloudizargari, Milad; Asghari, Mohammad Hossein; Goel, Ajay

doi:10.1016/j.bcp.2021.114714

Cited by 20 publications

(12 citation statements)

References 141 publications

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“…They function as a means of intercellular communication [ 1 , 2 , 3 , 4 ] and are involved in several physiological and pathological contexts, such as in embryogenesis [ 5 , 6 , 7 , 8 , 9 ], neuronal communication [ 10 ], blood coagulation [ 11 , 12 ], inflammation [ 13 , 14 ], tumorigenesis [ 1 , 15 ], and horizontal gene transfer [ 7 , 8 , 16 ]. In recent decades, EVs have been extensively studied for their potential clinical utility: as biomarkers to track the progression of various diseases, as drugs, or as vectors for drug-delivery [ 4 , 17 , 18 ]. However, the breakthrough from potential to practical application has been hindered by technical difficulties [ 19 , 20 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Stability of Erythrocyte-Derived Nanovesicles Assessed by Light Scattering and Electron Microscopy

Božič

Hočevar

Kisovec

et al. 2021

IJMS

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Extracellular vesicles (EVs) are gaining increasing amounts of attention due to their potential use in diagnostics and therapy, but the poor reproducibility of the studies that have been conducted on these structures hinders their breakthrough into routine practice. We believe that a better understanding of EVs stability and methods to control their integrity are the key to resolving this issue. In this work, erythrocyte EVs (hbEVs) were isolated by centrifugation from suspensions of human erythrocytes that had been aged in vitro. The isolate was characterised by scanning (SEM) and cryo-transmission electron microscopy (cryo-TEM), flow cytometry (FCM), dynamic/static light scattering (LS), protein electrophoresis, and UV-V spectrometry. The hbEVs were exposed to various conditions (pH (4–10), osmolarity (50–1000 mOsm/L), temperature (15–60 °C), and surfactant Triton X-100 (10–500 μM)). Their stability was evaluated by LS by considering the hydrodynamic radius (Rh), intensity of scattered light (I), and the shape parameter (ρ). The morphology of the hbEVs that had been stored in phosphate-buffered saline with citrate (PBS–citrate) at 4 °C remained consistent for more than 6 months. A change in the media properties (50–1000 mOsm/L, pH 4–10) had no significant effect on the Rh (=100–130 nm). At pH values below 6 and above 8, at temperatures above 45 °C, and in the presence of Triton X-100, hbEVs degradation was indicated by a decrease in I of more than 20%. Due to the simple preparation, homogeneous morphology, and stability of hbEVs under a wide range of conditions, they are considered to be a suitable option for EV reference material.

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Section: Introductionmentioning

confidence: 99%

Stability of Erythrocyte-Derived Nanovesicles Assessed by Light Scattering and Electron Microscopy

Božič

Hočevar

Kisovec

et al. 2021

IJMS

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“…Indeed, as they carry cell-specific markers, engineered EVs are primed to become the next generation of cell-specific drug delivery systems overcoming considerable side-effects associated with other drugs. In addition, one needs to consider the source of EVs as it can affect membrane composition and consequently change their homing capacity and biological function [ 47 ]. Thus, spontaneously-released EVs collected from an individual patient can open new therapeutic avenues for various brain disorders in the era of Precision medicine and personalized treatment.…”

Section: Discussionmentioning

confidence: 99%

A novel isolation method for spontaneously released extracellular vesicles from brain tissue and its implications for stress-driven brain pathology

et al. 2023

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Background Extracellular vesicles (EVs), including small EVs (sEVs) such as exosomes, exhibit great potential for the diagnosis and treatment of brain disorders, representing a valuable tool for precision medicine. The latter demands high-quality human biospecimens, especially in complex disorders in which pathological and specimen heterogeneity, as well as diverse individual clinical profile, often complicate the development of precision therapeutic schemes and patient-tailored treatments. Thus, the collection and characterization of physiologically relevant sEVs are of the utmost importance. However, standard brain EV isolation approaches rely on tissue dissociation, which can contaminate EV fractions with intracellular vesicles. Methods Based on multiscale analytical platforms such as cryo-EM, label-free proteomics, advanced flow cytometry, and ExoView analyses, we compared and characterized the EV fraction isolated with this novel method with a classical digestion-based EV isolation procedure. Moreover, EV biogenesis was pharmacologically manipulated with either GW4869 or picrotoxin to assess the validity of the spontaneous-release method, while the injection of labelled-EVs into the mouse brain further supported the integrity of the isolated vesicles. Results We hereby present an efficient purification method that captures a sEV-enriched population spontaneously released by mouse and human brain tissue. In addition, we tested the significance of the release method under conditions where biogenesis/secretion of sEVs was pharmacologically manipulated, as well as under animals’ exposure to chronic stress, a clinically relevant precipitant of brain pathologies, such as depression and Alzheimer’s disease. Our findings show that the released method monitors the drug-evoked inhibition or enhancement of sEVs secretion while chronic stress induces the secretion of brain exosomes accompanied by memory loss and mood deficits suggesting a potential role of sEVs in the brain response to stress and related stress-driven brain pathology. Conclusions Overall, the spontaneous release method of sEV yield may contribute to the characterization and biomarker profile of physiologically relevant brain-derived sEVs in brain function and pathology.

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“…Recently, great interest has been expressed in EVs due to their wide variety of therapeutic applications, since they can be used as effective drug carriers. One of the greatest advantages of EVs, when they are used as natural carriers, is that they can load both hydrophobic and hydrophilic drugs [ 95 ].…”

Section: Bioavailability Improvementsmentioning

confidence: 99%

Bioavailability Improvement Strategies for Icariin and Its Derivates: A Review

Szabó

Rácz

Dulf

2022

IJMS

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In recent years, there has been considerable interest in icariin (ICA) and its derivates, icariside II (ICS) and icaritin (ICT), due to their wide range of potential applications in preventing cancer, cardiovascular disease, osteoporosis, delaying the effects of Alzheimer’s disease, treating erectile dysfunction, etc. However, their poor water solubility and membrane permeability, resulting in low bioavailability, dampens their potential beneficial effects. In this regard, several strategies have been developed, such as pharmaceutical technologies, structural transformations, and absorption enhancers. All these strategies manage to improve the bioavailability of the above-mentioned flavonoids, thus increasing their concentration in the desired places. This paper focuses on gathering the latest knowledge on strategies to improve bioavailability for enhancing the efficacy of icariin, icariside II, and icaritin. We conclude that there is an opportunity for many further improvements in this field. To the best of our knowledge, no such review articles scoping the bioavailability improvement of icariin and its derivates have been published to date. Therefore, this paper can be a good starting point for all those who want to deepen their understanding of the field.

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The therapeutic triad of extracellular vesicles: As drug targets, as drugs, and as drug carriers

Cited by 20 publications

References 141 publications

Stability of Erythrocyte-Derived Nanovesicles Assessed by Light Scattering and Electron Microscopy

Stability of Erythrocyte-Derived Nanovesicles Assessed by Light Scattering and Electron Microscopy

A novel isolation method for spontaneously released extracellular vesicles from brain tissue and its implications for stress-driven brain pathology

Bioavailability Improvement Strategies for Icariin and Its Derivates: A Review

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