Exosomes and Exosome-Inspired Vesicles for Targeted Drug Delivery

Antimisiaris, Sophia G.; Mourtas, Spyridon; Marazioti, Antonia

doi:10.20944/preprints201810.0507.v1

Cited by 155 publications

(125 citation statements)

References 140 publications

(159 reference statements)

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“…Biomimetic nanomaterials have been extensively studied as drug delivery vectors, such as exosomes . Exosomes are a type of micro vesicle secreted by cells, which can transfer internal substances to surrounding cells efficiently through rich adhesion proteins interacting with cell membrane . Based on the above, we selected HFL‐1 cells as the maternal cells for the source of exosomes, which were characterized by DLS and TEM; the results showed that the average particle size was 88.45 ± 19.53 nm, with uniform size and typical vesicular structure.…”

Section: Discussionmentioning

confidence: 99%

Targeted exosome‐encapsulated erastin induced ferroptosis in triple negative breast cancer cells

et al. 2019

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Ferroptosis is an iron‐dependent, lipid peroxide‐driven cell death caused by inhibition of the cystine/glutamate transporter, which is of importance for the survival of triple‐negative breast cancer (TNBC) cells. Erastin is a low molecular weight chemotherapy drug that induces ferroptosis; however, poor water solubility and renal toxicity have limited its application. Exosomes, as drug delivery vehicles with low immunogenicity, high biocompatibility and high efficiency, have attracted increasing attention in recent years. Herein, we developed a formulation of erastin‐loaded exosomes labeled with folate (FA) to form FA‐vectorized exosomes loaded with erastin (erastin@FA‐exo) to target TNBC cells with overexpression of FA receptors. The characterization, drug release, internalization and anti–tumor effect in vitro of erastin@FA‐exo were determined. Erastin@FA‐exo could increase the uptake efficiency of erastin into MDA‐MB‐231 cells; compared with erastin@exo and free erastin, erastin@FA‐exo has a better inhibitory effect on the proliferation and migration of MDA‐MB‐231 cells. Furthermore, erastin@FA‐exo promoted ferroptosis with intracellular depletion of glutathione and reactive oxygen species overgeneration. Western blot analyses revealed that erastin@FA‐exo suppressed expression of glutathione peroxidase 4 (GPX4) and upregulated expression of cysteine dioxygenase (CDO1). We conclude that targeting and biocompatibility of exosome‐based erastin preparations provide an innovative and powerful delivery platform for anti–cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Targeted exosome‐encapsulated erastin induced ferroptosis in triple negative breast cancer cells

et al. 2019

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“…First, given that EVs are only ϳ40 nm to 1 m in size, the type and amount of cargo able to be loaded are limited; and therefore, therapeutic approaches may need to be in the nanoscale range. To date, engineered EVs have successfully been loaded with 70 -250 kDa molecules, although the current methods have had low success in generating a large yield of viable EVs (Antimisiaris et al, 2018). Second, the targeted delivery method must be validated for selectivity and off-target effects.…”

Section: Ev Delivery Into the Brainmentioning

confidence: 99%

NeuroEVs: Characterizing Extracellular Vesicles Generated in the Neural Domain

Fowler

2019

J. Neurosci.

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Intercellular communication has recently been shown to occur via transfer of cargo loaded within extracellular vesicles (EVs). Present within all biofluids of the body, EVs can contain various signaling factors, including coding and noncoding RNAs (e.g., mRNA, miRNA, lncRNA, snRNA, tRNA, yRNA), DNA, proteins, and enzymes. Multiple types of cells appear to be capable of releasing EVs, including cancer, stem, epithelial, immune, glial, and neuronal cells. However, the functional impact of these circulating signals among neural networks within the brain has been difficult to establish given the complexity of cellular populations involved in release and uptake, as well as inherent limitations of examining a biofluid. In this brief commentary, we provide an analysis of the conceptual and technical considerations that limit our current understanding of signaling mediated by circulating EVs relative to their impact on neural function.

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“…However, sub-optimal delivery systems have hindered their progress into clinical settings. Exosomes offer a non-toxic and non-immunogenic delivery systems, however, efficiency of their drug-loading and retention is not sufficient to have substantial therapeutic effects in vivo 32,33 . Previously published studies have shown that intravenously injected exosomes are rapidly cleared from the blood and accumulate in lung, liver and spleen 54,55 .…”

Section: Discussionmentioning

confidence: 99%

“…Previously published studies have shown that intravenously injected exosomes are rapidly cleared from the blood and accumulate in lung, liver and spleen 54,55 . Industrial scale production of exosomes is a big hurdle to overcome before exosomes are tested in the clinic for treatment of a vast array of diseases 32 . In addition, there are no published results of trials, which used exosomes as miR carriers yet 56 .…”

Section: Discussionmentioning

confidence: 99%

“…Mesenchymal stem cells (MSCs) have been demonstrated to be a safe and effective delivery vehicle for miRs, due to their ability to specifically target cancer cells and to transfer molecules via exosomal trafficking 32,33 . We hypothesized that MSC-shed exosomes will serve as carriers for anti-miR-21 and these MSC can be utilized to deliver miRzip-21 to the tumors in vivo (Fig.…”

Section: Aav-mirzip-21 But Not Msc-mirzip-21 Attenuates Cancer Growthmentioning

confidence: 99%

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Simultaneous downregulation of miR-21 and upregulation of miR-7 has anti-tumor efficacy

Bhere

Arghiani

Lechtich

et al. 2020

Sci Rep

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Dysregulation of miRNA expression has been implicated in cancer. Numerous strategies have been explored to modulate miR but sub-optimal delivery and inability to concurrently target multiple pathways involved in tumor progression have limited their efficacy. In this study, we explored the potential co-modulation of upregulated miR-21 and downregulated miR-7 to enhance therapeutic outcomes in heterogenic tumor types. We first engineered lentiviral (LV) and adeno-associated viral (AAV) vectors that preferentially express anti-sense miR against miR-21(miRzip-21) and show that modulating miR-21 via miRzip extensively targets tumor cell proliferation, migration and invasion in vitro in a broad spectrum of cancer types and has therapeutic efficacy in vivo. Next, we show a significantly increased expression of caspase-mediated apoptosis by simultaneously downregulating miR-21 and upregulating miR-7 in different tumor cells. In vivo co-treatment with AAV-miRzip-21 and AAV-miR-7 in mice bearing malignant brain tumors resulted in significantly decreased tumor burden with a corresponding increase in survival. To our knowledge, this is the first study that demonstrates the therapeutic efficacy of simultaneously upregulating miR-7 and downregulating miR-21 and establishes a roadmap towards clinical translation of modulating miRs for various cancer types.

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Exosomes and Exosome-Inspired Vesicles for Targeted Drug Delivery

Cited by 155 publications

References 140 publications

Targeted exosome‐encapsulated erastin induced ferroptosis in triple negative breast cancer cells

Targeted exosome‐encapsulated erastin induced ferroptosis in triple negative breast cancer cells

NeuroEVs: Characterizing Extracellular Vesicles Generated in the Neural Domain

Simultaneous downregulation of miR-21 and upregulation of miR-7 has anti-tumor efficacy

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