Challenges in the development and establishment of exosome-based drug delivery systems

Wang, Jin; Chen, Derek; Ho, Emmanuel A.

doi:10.1016/j.jconrel.2020.10.020

Cited by 205 publications

(193 citation statements)

References 92 publications

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“…Nevertheless, clinical translation of natural exosomes has been challenging [ 114 ]. Major hurdles including large-scale production, standard purification protocols, characterization of complex composition, cargo loading, quality control and storage stability are in their way to products for therapeutic applications [ 115 ]. Mass production of exosomes may be achieved through the development of bioreactors [ 38 ]; however, as biological components, their standardized and reproducible production requires comprehensive control of genetic stability and culturing condition of producing cells; purification requires subtype identification and quantification of contaminants [ 116 ]; efficacy is dependent on drug loading efficiency and capacity [ 117 ]; storage of therapeutic exosomes is supposed to have high recovery without damage to exosome particles as well as their biological contents [ 118 , 119 ].…”

Section: Comparison Of Natural Exosomes and Artificial Exosomesmentioning

confidence: 99%

Artificial exosomes for translational nanomedicine

et al. 2021

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Exosomes are lipid bilayer membrane vesicles and are emerging as competent nanocarriers for drug delivery. The clinical translation of exosomes faces many challenges such as massive production, standard isolation, drug loading, stability and quality control. In recent years, artificial exosomes are emerging based on nanobiotechnology to overcome the limitations of natural exosomes. Major types of artificial exosomes include ‘nanovesicles (NVs)’, ‘exosome-mimetic (EM)’ and ‘hybrid exosomes (HEs)’, which are obtained by top-down, bottom-up and biohybrid strategies, respectively. Artificial exosomes are powerful alternatives to natural exosomes for drug delivery. Here, we outline recent advances in artificial exosomes through nanobiotechnology and discuss their strengths, limitations and future perspectives. The development of artificial exosomes holds great values for translational nanomedicine.

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Section: Comparison Of Natural Exosomes and Artificial Exosomesmentioning

confidence: 99%

Artificial exosomes for translational nanomedicine

et al. 2021

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“…The documented roles of cell-secreted extracellular vesicles (EVs) in intercellular communication via the transfer of their innate cargo make them attractive drug delivery carriers [1][2][3][4][5][6][7][8][9][10][11]. The subtypes of EVs vary in particle diameters, among other factors, with the larger, 100-1000 nm microvesicles (MVs), and the smaller, 50 -150 nm exosomes (EXOs) being secreted via different biogenesis pathways [1,[6][7][8][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Microvesicles Transfer Mitochondria and Increase Mitochondrial Function in Brain Endothelial Cells

D’Souza

Burch

Dave

et al. 2021

Preprint

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Extracellular vesicles (EVs) such as exosomes (EXOs) and microvesicles (MVs) are promising carriers for the delivery of biologic drugs such as nucleic acids and proteins. We have demonstrated, for the first time, that EVs derived from hCMEC/D3: a human brain endothelial cell (BEC) line transfer polarized mitochondria to recipient BECs in culture and to neurons in mice acute brain cortical and hippocampal slices. This mitochondrial transfer increased ATP levels by 100 to 200-fold (relative to untreated cells) in the recipient BECs exposed to oxygen-glucose deprivation, an in vitro model of cerebral ischemia. Our previous studies suggested that EXOs, the smaller vesicle subpopulation, derived from a macrophage cell line (RAW264.7) load more exogenous plasmid DNA compared to the larger MVs and the RAW-derived EXOs also demonstrated greater transfection in the recipient BECs compared to EXOs derived from the homotypic hCMEC/D3 BECs. Proteomic analysis of EVs indicated that RAW-EVs are preferentially enriched with proteins that are involved in the trafficking of DNA-containing particles from the cytoplasm towards the nucleus. Intriguingly, although the heterotypic macrophage-derived EVs demonstrated increased transfection in the recipient BECs; the homotypic, BEC-derived EVs demonstrated a greater selectivity to transfer polarized mitochondria and increase endothelial cell survival under ischemic conditions.

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“…Electron microscopy (EM) is necessary to characterize the morphology of exosomes since particles smaller than 300 nm are too small to be observed with optical methods [313,314]. When studying biological samples, two types of EM are widely used, namely transmission electron microscopy (TEM) and scanning electron microscopy (SEM) [315]. The former is considered the gold standard for studying exosome morphology.…”

Section: External Characterization Detection Of Exosome Morphologymentioning

confidence: 99%

“…Unfortunately, the benefits of high resolution can easily be outweighed by the disadvantages related to sample preparation, as they must be fixed and dehydrated prior to their observation by TEM. In addition, image acquisition is performed under vacuum conditions which can further alter the morphology of exosomes [315].…”

Section: External Characterization Detection Of Exosome Morphologymentioning

confidence: 99%

Exosomes: Potential Disease Biomarkers and New Therapeutic Targets

et al. 2021

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Exosomes are extracellular vesicles released by cells, both constitutively and after cell activation, and are present in different types of biological fluid. Exosomes are involved in the pathogenesis of diseases, such as cancer, neurodegenerative diseases, pregnancy disorders and cardiovascular diseases, and have emerged as potential non-invasive biomarkers for the detection, prognosis and therapeutics of a myriad of diseases. In this review, we describe recent advances related to the regulatory mechanisms of exosome biogenesis, release and molecular composition, as well as their role in health and disease, and their potential use as disease biomarkers and therapeutic targets. In addition, the advantages and disadvantages of their main isolation methods, characterization and cargo analysis, as well as the experimental methods used for exosome-mediated drug delivery, are discussed. Finally, we present potential perspectives for the use of exosomes in future clinical practice.

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Challenges in the development and establishment of exosome-based drug delivery systems

Cited by 205 publications

References 92 publications

Artificial exosomes for translational nanomedicine

Artificial exosomes for translational nanomedicine

Microvesicles Transfer Mitochondria and Increase Mitochondrial Function in Brain Endothelial Cells

Exosomes: Potential Disease Biomarkers and New Therapeutic Targets

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