Extracellular vesicles as a drug delivery system: A systematic review of preclinical studies

Castilla, Pol Escudé Martinez de; Tong, Lingjun; Huang, Chenyuan; Sofias, Alexandros Marios; Pastorin, Giorgia; Chen, Xiaoyuan; Storm, Gert; Schiffelers, Raymond M.; Wang, Jiong‐Wei

doi:10.1016/j.addr.2021.05.011

Cited by 127 publications

(111 citation statements)

References 309 publications

(243 reference statements)

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“…Along with the rapid growth in nanobiotechnology, the research of exosomes has been advancing from biology [ 32 , 106 ] to biomarkers [ 107 , 108 ] and nanomedicines [ 109 ] over the past decade. For drug delivery, exosomes have shown various advantages compared with conventional synthetic materials such as liposomes [ 110 ]. The therapeutic potential of exosomes-mediated drug delivery are still in tests of preliminary clinical trials (pancreatic cancer: NCT03608631; acute ischemic stroke: NCT03384433; colon cancer: NCT01294072), while the efficacy of cell-derived exosome-like vesicles has been evidenced in several pilot trials [ 111 – 113 ].…”

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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“…Extracellular vesicles (EVs) are cell-derived particles delimited by lipid membranes that vary in size from 30 to 1000 nm in diameter. They are produced by cells from all three domains of life [4] and have different biological functions and cargo, composed mostly of protein, nucleic acids, and carbohydrates. EVs have been identified in more than 20 yeasts and filamentous fungal species, although EVs from human pathogens such as Candida albicans [5], and Cryptococcus neoformans [6] are the best characterized.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles from Fusarium graminearum Contain Protein Effectors Expressed during Infection of Corn

Garcia-Ceron

McKenna

Brain

et al. 2021

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Fusarium graminearum (Fgr) is a devastating filamentous fungal pathogen that causes diseases in cereals, while producing mycotoxins that are toxic for humans and animals, and render grains unusable. Low efficiency in managing Fgr poses a constant need for identifying novel control mechanisms. Evidence that fungal extracellular vesicles (EVs) from pathogenic yeast have a role in human disease led us to question whether this is also true for fungal plant pathogens. We separated EVs from Fgr and performed a proteomic analysis to determine if EVs carry proteins with potential roles in pathogenesis. We revealed that protein effectors, which are crucial for fungal virulence, were detected in EV preparations and some of them did not contain predicted secretion signals. Furthermore, a transcriptomic analysis of corn (Zea mays) plants infected by Fgr revealed that the genes of some of the effectors were highly expressed in vivo, suggesting that the Fgr EVs are a mechanism for the unconventional secretion of effectors and virulence factors. Our results expand the knowledge on fungal EVs in plant pathogenesis and cross-kingdom communication, and may contribute to the discovery of new antifungals.

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“…Importantly, the tissue distribution and clearance of EVs might be influenced by the route of administration [ 85 ]. IV administration has been the most popular administration route studied up until now and is still gaining interest [ 126 ]. In general, the majority of the IV injected EVs rapidly accumulates in the organs of the reticuloendothelial system (RES), such as liver and spleen, with a rather small proportion of the injected dose reaching the brain after systemic administration [ 85 , 127 , 128 , 129 ].…”

Section: Extracellular Vesicles As Drug Delivery Vehiclementioning

confidence: 99%

“…In general, one of the most studied unmodified EV types is undoubtedly the mesenchymal stem cell (MSC) derived EV [ 126 ]. MSCs and their secretions, including EVs, are known to have intrinsic neuroprotective, regenerative and anti-inflammatory properties [ 132 , 133 ].…”

Section: Extracellular Vesicles As Drug Delivery Vehiclementioning

confidence: 99%

“…The choice of EV dose, administration route and administration frequency influences EV biodistribution and therapeutic efficacy. Indeed, while IV administration has been the most explored administration route over the past decade [ 126 ], other systemic or local administration routes lead to different pharmacokinetics and pharmacodynamics, which might be more or less suitable in specific disease contexts. On top of that, the EV dose depends on the applied EV isolation and quantification method which enhances variation due to the wealth of available techniques.…”

Section: Practical Considerations Towards Evs As a Therapeutic Delivery Platform To The Brainmentioning

confidence: 99%

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Special delEVery: Extracellular Vesicles as Promising Delivery Platform to the Brain

2021

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The treatment of central nervous system (CNS) pathologies is severely hampered by the presence of tightly regulated CNS barriers that restrict drug delivery to the brain. An increasing amount of data suggests that extracellular vesicles (EVs), i.e., membrane derived vesicles that inherently protect and transfer biological cargoes between cells, naturally cross the CNS barriers. Moreover, EVs can be engineered with targeting ligands to obtain enriched tissue targeting and delivery capacities. In this review, we provide a detailed overview of the literature describing a natural and engineered CNS targeting and therapeutic efficiency of different cell type derived EVs. Hereby, we specifically focus on peripheral administration routes in a broad range of CNS diseases. Furthermore, we underline the potential of research aimed at elucidating the vesicular transport mechanisms across the different CNS barriers. Finally, we elaborate on the practical considerations towards the application of EVs as a brain drug delivery system.

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Extracellular vesicles as a drug delivery system: A systematic review of preclinical studies

Cited by 127 publications

References 309 publications

Artificial exosomes for translational nanomedicine

Artificial exosomes for translational nanomedicine

Extracellular Vesicles from Fusarium graminearum Contain Protein Effectors Expressed during Infection of Corn

Special delEVery: Extracellular Vesicles as Promising Delivery Platform to the Brain

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