Delivery of Small Interfering RNA to Inhibit Vascular Endothelial Growth Factor in Zebrafish Using Natural Brain Endothelia Cell-Secreted Exosome Nanovesicles for the Treatment of Brain Cancer

Yang, Tianzhi; Fogarty, Brittany; LaForge, Bret; Aziz, Salma; Pham, Thuy Trang; Lai, Leanne; Bai, Shuhua

doi:10.1208/s12248-016-0015-y

Cited by 168 publications

(99 citation statements)

References 51 publications

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“…For example, several published reports have demonstrated that exosomes are capable of crossing the blood-brain barrier (BBB) when active neuroinflammation is present. [47][48][49] Neuroinflammatory cascades often result in the compromised integrity of the BBB, thereby allowing for large macromolecules and even cells to enter from the periphery. 50,51 In addition, some methods of manufacturing and labeling MEX use extended processing times, which may decrease their resulting functional properties.…”

Section: Mex Biodistributionmentioning

confidence: 99%

Preclinical translation of exosomes derived from mesenchymal stem/stromal cells

et al. 2019

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Exosomes are nanovesicles secreted by virtually all cells. Exosomes mediate the horizontal transfer of various macromolecules previously believed to be cell-autonomous in nature, including nonsecretory proteins, various classes of RNA, metabolites, and lipid membrane-associated factors. Exosomes derived from mesenchymal stem/stromal cells (MSCs) appear to be particularly beneficial for enhancing recovery in various models of disease. To date, there have been more than 200 preclinical studies of exosome-based therapies in a number of different animal models. Despite a growing number of studies reporting the therapeutic properties of MSC-derived exosomes, their underlying mechanism of action, pharmacokinetics, and scalable manufacturing remain largely outstanding questions. Here, we review the global trends associated with preclinical development of MSC-derived exosome-based therapies, including immunogenicity, source of exosomes, isolation methods, biodistribution, and disease categories tested to date. Although the in vivo data assessing the therapeutic properties of MSC-exosomes published to date are promising, several outstanding questions remain to be answered that warrant further preclinical investigation.

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Section: Mex Biodistributionmentioning

confidence: 99%

Preclinical translation of exosomes derived from mesenchymal stem/stromal cells

et al. 2019

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“…Exosomes are a sub-population of specialized membranous extracellular vesicles derived from endocytotic compartments, are 30 to 100 nm in size, and are actively secreted by almost all cell types [95]. The exosomes ability to cross the BBB has been studied in zebrafish and mouse models [96,97]. Only exosomes isolated from brain endothelial cells could cross the BBB and deliver cargo into the CNS suggesting potential homo-tropism for the tissue of origin [97].…”

Section: Nanocarriers Nanoparticles and Vectorsmentioning

confidence: 99%

“…The exosomes ability to cross the BBB has been studied in zebrafish and mouse models [96,97]. Only exosomes isolated from brain endothelial cells could cross the BBB and deliver cargo into the CNS suggesting potential homo-tropism for the tissue of origin [97].…”

Section: Nanocarriers Nanoparticles and Vectorsmentioning

confidence: 99%

Overcoming the Blood–Brain Barrier. Challenges and Tricks for CNS Drug Delivery

2019

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Treatment of certain central nervous system disorders, including different types of cerebral malignancies, is limited by traditional oral or systemic administrations of therapeutic drugs due to possible serious side effects and/or lack of the brain penetration and, therefore, the efficacy of the drugs is diminished. During the last decade, several new technologies were developed to overcome barrier properties of cerebral capillaries. This review gives a short overview of the structural elements and anatomical features of the blood–brain barrier. The various in vitro (static and dynamic), in vivo (microdialysis), and in situ (brain perfusion) blood–brain barrier models are also presented. The drug formulations and administration options to deliver molecules effectively to the central nervous system (CNS) are presented. Nanocarriers, nanoparticles (lipid, polymeric, magnetic, gold, and carbon based nanoparticles, dendrimers, etc.), viral and peptid vectors and shuttles, sonoporation and microbubbles are briefly shown. The modulation of receptors and efflux transporters in the cell membrane can also be an effective approach to enhance brain exposure to therapeutic compounds. Intranasal administration is a noninvasive delivery route to bypass the blood–brain barrier, while direct brain administration is an invasive mode to target the brain region with therapeutic drug concentrations locally. Nowadays, both technological and mechanistic tools are available to assist in overcoming the blood–brain barrier. With these techniques more effective and even safer drugs can be developed for the treatment of devastating brain disorders.

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“…In addition, a recent study has used the zebrafish embryo model for testing their potential in drug delivery. 115,116 Although preliminary, these studies suggest that the zebrafish embryo could be a very useful model for studying the biology of exosomes in the near future.…”

Section: Outstanding Open Questionsmentioning

confidence: 98%

Going live with tumor exosomes and microvesicles

Hyenne

Lefèbvre

Goetz

2017

Cell Adhesion & Migration

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Tumor extracellular vesicles (EVs), including exosomes, emerged as key drivers of the pro-tumorigenic dialog between the tumor mass and its microenvironment by mediating long and short distance communication. In vitro studies defined the capacity of tumor EVs to modify the phenotypes of stromal and tumor cells. These studies are now supported by a growing number of functional in vivo experiments. Remarkably, they allowed the identification of a new role for tumor EVs in priming the pre-metastatic niches (PMN). Several molecules transported in tumor EVs (RNAs and proteins) have recently been found to be essential for tumor progression and metastasis in vivo. In parallel, novel EV labeling and tracking strategies have very recently allowed the first descriptions of tumor EVs in vivo and pave the way for a better understanding of their function in realistic pathophysiological contexts. Here, we review the functional approaches and the recent progress in in vivo imaging of EVs, which have refined our understanding of the role played by tumor EVs. Finally, we emphasize the remaining challenges and open questions related to the biology of tumor EVs.

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Delivery of Small Interfering RNA to Inhibit Vascular Endothelial Growth Factor in Zebrafish Using Natural Brain Endothelia Cell-Secreted Exosome Nanovesicles for the Treatment of Brain Cancer

Cited by 168 publications

References 51 publications

Preclinical translation of exosomes derived from mesenchymal stem/stromal cells

Preclinical translation of exosomes derived from mesenchymal stem/stromal cells

Overcoming the Blood–Brain Barrier. Challenges and Tricks for CNS Drug Delivery

Going live with tumor exosomes and microvesicles

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