Using exosomes, naturally-equipped nanocarriers, for drug delivery

Batrakova, Elena V.; Kim, Myoung Soo

doi:10.1016/j.jconrel.2015.07.030

Cited by 867 publications

(686 citation statements)

References 128 publications

(173 reference statements)

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“…There are several advantages of the use of EVs as opposed to cells. These include their ability to cross the blood-brain barrier and deliver various therapeutic factors to the brain (25,26); amenability for engineering to package specific mRNAs, miRNAs, and proteins (26,27); and minimal risk for developing tumors or causing thrombosis. Future studies will be focused on determining whether the extent of neuroprotective, antiinflammatory, neurogenic, cognitive, and memory-protective effects mediated by A1-exosomes is adequate to prevent the evolution of SE-induced initial precipitating injury into a chronic epileptic state.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, several studies suggest that therapeutic benefits of MSC administration are largely explained by paracrine effects mediated by soluble factors or EVs secreted by MSCs (21)(22)(23)(24). Furthermore, EVs can cross the blood-brain barrier and deliver various therapeutic factors to the brain (25,26). EVs containing a multitude of mRNAs, miRNAs, and proteins (26,27) can be harvested, characterized, and banked from MSCs obtained from…”

mentioning

confidence: 99%

“…Furthermore, EVs can cross the blood-brain barrier and deliver various therapeutic factors to the brain (25,26). EVs containing a multitude of mRNAs, miRNAs, and proteins (26,27) can be harvested, characterized, and banked from MSCs obtained from…”

mentioning

confidence: 99%

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Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus

Long

Upadhya

Hattiangady

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

329

299

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Status epilepticus (SE), a medical emergency that is typically terminated through antiepileptic drug treatment, leads to hippocampus dysfunction typified by neurodegeneration, inflammation, altered neurogenesis, as well as cognitive and memory deficits. Here, we examined the effects of intranasal (IN) administration of extracellular vesicles (EVs) secreted from human bone marrowderived mesenchymal stem cells (MSCs) on SE-induced adverse changes. The EVs used in this study are referred to as A1-exosomes because of their robust antiinflammatory properties. We subjected young mice to pilocarpine-induced SE for 2 h and then administered A1-exosomes or vehicle IN twice over 24 h. The A1-exosomes reached the hippocampus within 6 h of administration, and animals receiving them exhibited diminished loss of glutamatergic and GABAergic neurons and greatly reduced inflammation in the hippocampus. Moreover, the neuroprotective and antiinflammatory effects of A1-exosomes were coupled with long-term preservation of normal hippocampal neurogenesis and cognitive and memory function, in contrast to waned and abnormal neurogenesis, persistent inflammation, and functional deficits in animals receiving vehicle. These results provide evidence that IN administration of A1-exosomes is efficient for minimizing the adverse effects of SE in the hippocampus and preventing SE-induced cognitive and memory impairments.status epilepticus | memory dysfunction | neuroinflammation | exosomes | adult neurogenesis S tatus epilepticus (SE) is a grave medical crisis that requires swift remedy through all age groups (1, 2). It can produce substantial neurodegeneration, blood-brain barrier disruption, and inflammation in the hippocampus if not extinguished quickly by antiepileptic drug (AED) treatment (3-5). An episode of extended SE is sufficient to cause chronic hippocampus dysfunction, exemplified by persistent inflammation with activation of microglia and monocyte infiltration, loss of sizable fractions of several subclasses of inhibitory interneurons, aberrant and waned neurogenesis, hippocampus-dependent cognitive and memory impairments, and chronic epilepsy (5-12). Numerous situations such as head trauma, stroke, Alzheimer's disease, brain tumor, and encephalitis can engender SE. Although administration of AEDs leads to termination of SE in most instances, it does not thwart the evolution of SE into chronic epilepsy (13-16). A multitude of changes ensue in the hippocampus after an episode of SE, which evolve over a period of months, years, or even decades, and result in chronic epilepsy when they have reached certain thresholds (11,17,18). Hence, there is an urgent need to find an adjuvant therapy with AEDs that not only provides neuroprotection and suppression of inflammation in the early phase after SE but also maintains normal neurogenesis, preserves cognitive and memory function, and thwarts epilepsy development in the chronic phase after SE. The i.v. administration of bone marrow-derived mononuclear cells (MNCs) or mesenchymal stem cells (...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus

Long

Upadhya

Hattiangady

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

329

299

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“…Up to date, exosomes have also been confirmed to be associated with immune regulation [19], to mediate communication within the tumor microenvironment [20] and to be naturally-equipped nanocarriers for drug delivery [21]. MiRNA-221 in exosomes from bone marrow mesenchymal stem cells could activate oncogenic activity in gastric cancer [22].…”

Section: Urinary Exosomes Proteomics Analysismentioning

confidence: 99%

High-purified Isolation and Proteomic Analysis of Urinary Exosomes from Healthy Persons

Yang¹,

Zhi²,

Liu³

et al. 2017

Nano BioMed ENG

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Urinary exosomes containing specific biomarkers have recently been considered as novel potential non-invasive candidates for renal disease diagnosis. However, the development of urinary exosomes in basic research and their subsequent diagnostic application are impeded by the lack of an efficient isolation method. One of the main challenges during urinary exosomes isolation is how to remove a large number of Tamm Horsfall proteins (around 92 kDa) and other biological components from exosome enrichment mixture. Herein, we report a facile and low-cost isolation method for highlypurified human urinary exosomes based on dialysis. The key protocol for exosome isolation includes only two steps: (1) Healthy person urines were collected. 10 mL urine in 300 kDa dialysis tubes was firstly dialyzed in phosphate-buffered saline solution three times for sequential nine hours; (2) The dialysis suspension was concentrated to 200 μL by using 100 kDa ultracentrifuge tubes to achieve urinary exosome isolation. For verification, the concentrated solution was examined by western blot, transmission electronic microscopy, atomic force microscopy and qNano, which demonstrated the highly-purified urinary exosomes were present. Furthermore, a total of 359 proteins were identified by the proteomic analysis of purified urinary exosomes from healthy persons. Those results demonstrated that highly-purified urinary exosomes could be achieved by our isolation method; 359 proteins were identified from healthy persons. Further works will focus on screening and identifying disease-related biomarkers from human urine exosomes for clinical diagnosis.

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“…This feature that NVs can carry cargoes safely has attracted the attention of researchers who develop biomaterial-based drugs [34]. Several remarkable approaches have been developed to prepare NVs with therapeutic agents (reviewed in [35]). The pre-treatments before the isolation of exosomes include 1) the incorporation of purified drugs into NVs from parental cells by ex vitro, 2) the use of NVs released from parental cells with drugs, and 3) the transfection of NVs from donor cells with drug-encoding DNA or therapeutic compounds.…”

Section: Mgmentioning

confidence: 99%

Nanovesicles: Diagnostic and Therapeutic Tools in Nanoscale Medicine

Kim

2016

Applied Science and Convergence Technology

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The use of nanovesicles (NVs) has contributed to nanotechnology in the development of new concept medicine to compete with diseases of deleterious and infectious to human health. Due to their properties of size, morphology, and biocompatibility NVs have great impact on public health especially in the development of new therapeutic and prophylaxis approaches in addition to the device for biosensors to diagnose human diseases. Recent data also strongly suggest that NVs are regarded as innovative materials in developing for vaccines and diagnostic tools. In this review, we focus on the basic concepts and recent applications of NVs to utilize or engineer them as therapeutic materials.

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Using exosomes, naturally-equipped nanocarriers, for drug delivery

Cited by 867 publications

References 128 publications

Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus

Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus

High-purified Isolation and Proteomic Analysis of Urinary Exosomes from Healthy Persons

Nanovesicles: Diagnostic and Therapeutic Tools in Nanoscale Medicine

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