Dopamine-loaded blood exosomes targeted to brain for better treatment of Parkinson's disease

Qu, Mengke; Lin, Qing; Huang, Luyi; Fu, Yao; Wang, Luyao; He, Shanshan; Fu, Yu; Yang, Shengyong; Zhang, Zhirong; Zhang, Ling; Sun, Xun

doi:10.1016/j.jconrel.2018.08.035

Cited by 416 publications

(296 citation statements)

References 40 publications

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“…Other potential advantages include the fact that EVs are biocompatible and self-derived, and therefore immunologically transparent. Moreover, EVs such as exosomes have the ability to cross the BBB, [87][88][89] and in a recent study, brain endothelial cell-derived exosomes were used as a drug carrier for treating brain cancer. 18 Further, to enhance the targeting ability of exosomes, their surfaces were functionalized with a peptide, which resulted in strong suppression of the inflammatory response and cellular apoptosis in the lesion region.…”

Section: Possible Treatment Of Cancer and Neurodegenerative Disordersmentioning

confidence: 99%

<p>Extracellular Vesicles As Nanomedicine: Hopes And Hurdles In Clinical Translation</p>

Burnouf

Agrahari

2019

IJN

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The clinical development of cell therapies is revealing that extracellular vesicles (EVs) may become very instrumental as subcellular therapeutic adjuncts in human medicine. EVs are released by various types of cells, grown in culture, such as mesenchymal stromal cells, or obtained from patients or allogeneic donors. Some EV populations (especially species of exosomes and shed microvesicles) exhibit inherent roles in cell-cell communication, thanks to their ca. 30~1000-nm nanosize and the physiological expression of cellspecific markers on their lipid bilayer membranes. Biomedical engineers are now attempting to exploit this cellular crosstalk capacity to use EVs as smart drug delivery systems that display substantial benefits in targeting, safety, and pharmacokinetics compared to synthetic nanocarriers. In parallel, the development of a set of nano-instrumentation, biochemical tools, and preclinical assays needed for optimal characterization of both naïve and drugloaded EVs is ongoing. Although many hurdles remain, owing to the complexity of EV populations, translation of this "subcellular therapy" platform into reality is at hand and may soon change the landscape of the therapeutic arsenal in place to treat human degenerative and metabolic pathologies as well as diseases like cancer. This article provides objective opinions, balanced between unrealistic hopes of the capacity of EVs to resolve multiple clinical issues and concrete hurdles that have to be overcome to ensure that EVs are not lost in the translation phase, so that EVs can fulfill their promise by becoming a reliable therapeutic modality.

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Section: Possible Treatment Of Cancer and Neurodegenerative Disordersmentioning

confidence: 99%

<p>Extracellular Vesicles As Nanomedicine: Hopes And Hurdles In Clinical Translation</p>

Burnouf

Agrahari

2019

IJN

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“…Dopamine-loaded exosomes derived from the blood of mice were used to deliver drugs across the BBB with lower systemic toxicity compared to i.v. administration of naked dopamine [152]. As an alternative approach, Haney et al (2015) circumvented the BBB, using intranasal delivery to successfully administer the catalase-loaded macrophage-derived exosomes to the brain of mice with a model of PD, resulting in significant neuroprotective effects [131].…”

Section: Exosomesmentioning

confidence: 99%

Peptide based drug delivery systems to the brain

Islam

Leach

Smith³

et al. 2020

Nano Express

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With estimated worldwide cost over $1 trillion just for dementia, diseases of the central nervous system pose a major problem to health and healthcare systems, with significant socio-economic implications for sufferers and society at large. In the last two decades, numerous strategies and technologies have been developed and adapted to achieve drug penetration into the brain, evolving alongside our understanding of the physiological barriers between the brain and surrounding tissues. The blood brain barrier (BBB) has been known as the major barrier for drug delivery to the brain. Both invasive and minimally-invasive approaches have been investigated extensively, with the minimallyinvasive approaches to drug delivery being more suitable. Peptide based brain targeting has been explored extensively in the last two decades. In this review paper, we focused on self-assembled peptides, shuttle peptides and nanoparticles drug delivery systems decorated/conjugated with peptides for brain penetration.Abbreviations

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“…Loaded exosomes could transfer dopamine to damaged cells of the striatum and substantia nigra areas, and its neuronal distribution was higher than that of free dopamine (> 15 folds) due to the receptor-mediated uptake by transferrin and transferrin receptor (TfR). The safe dopamine-loaded exosome showed powerful therapeutic effects to decrease brain inflammation (74). In another experimental study, exosomes derived from mouse embryonic derived were loaded with curcumin to promote angiogenesis in the mouse model of ischemia-reperfusion (IR).…”

Section: Brain Targeting By Drug Delivery System-based Exosomesmentioning

confidence: 99%

Mesenchymal Cell-Derived Exosomes as Novel Useful Candidates for Drug Delivery

Einabadi

Kargar

et al. 2020

Arch Neurosci

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Mesenchymal stem cells (MSCs) are one of the most accessible adult multipotent stem cells that can be harvested from various tissues. The tissue regeneration field uses MSCs because of their therapeutic potential in tissue damage repair, inflammation suppression, and anti-tumor therapies, relying on their targeted homing and differentiation capability into specialized cells. It is proposed that the paracrine activities of MSCs, including secretory trophic factors, survival signals, and extracellular vesicle release, are the principal mechanism to mediate MSCs function. Current studies show that exosomes secreted by MSCs may also contribute to MSCs' physiological function. Indeed, they can be introduced as hopeful novel candidates for drug delivery due to their nanoscale naturally-occurring structure, more stability, less immunogenicity, and the ability to pass through biological barriers without rejection to deliver their cargos to recipient cells and tissues. Moreover, exosomes may anticipate beneficial nanocarrier vehicles in targeted drug delivery systems.

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Dopamine-loaded blood exosomes targeted to brain for better treatment of Parkinson's disease

Cited by 416 publications

References 40 publications

<p>Extracellular Vesicles As Nanomedicine: Hopes And Hurdles In Clinical Translation</p>

<p>Extracellular Vesicles As Nanomedicine: Hopes And Hurdles In Clinical Translation</p>

Peptide based drug delivery systems to the brain

Mesenchymal Cell-Derived Exosomes as Novel Useful Candidates for Drug Delivery

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