A New Approach for Loading Anticancer Drugs Into Mesenchymal Stem Cell-Derived Exosome Mimetics for Cancer Therapy

Kalimuthu, S; Gangadaran, Prakash; Rajendran, Ramya Lakshmi; Zhu, Li; Oh, Ji Min; Lee, Ho Won; Gopal, Arunnehru; Baek, Se Hwan; Jeong, Shin Young; Lee, Sang‐Woo; Lee, Jaetae; Ahn, Byeong‐Cheol

doi:10.3389/fphar.2018.01116

Cited by 206 publications

(161 citation statements)

References 40 publications

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“…While Bcl2 is regarded as a negative marker for exosomes, M‐NVs were found to contain an abundant amount of Bcl2 protein (Figure B). Because the overexpression of Bcl2 has been shown to protect immortalized cells from chemically induced cell death and together with previous studies reporting a low abundance of the apoptotic inducer, Cytochrome C, in M‐NVs, it is intriguing to speculate that M‐NVs could be useful as potential antiapoptotic agents. Overall, M‐NVs can mimic the ultrastructure of exosomes but do not display an abundance of proteins that are typically involved in exosomes biogenesis.…”

Section: Resultssupporting

confidence: 82%

Proteomic and Post‐Translational Modification Profiling of Exosome‐Mimetic Nanovesicles Compared to Exosomes

et al. 2019

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Issues associated with upscaling exosome production for therapeutic use may be overcome through utilizing artificial exosomes. Cell‐derived mimetic nanovesicles (M‐NVs) are a potentially promising alternative to exosomes for clinical applicability, demonstrating higher yield without incumbent production and isolation issues. Although several studies have shown that M‐NVs have similar morphology, size and therapeutic potential compared to exosomes, comprehensive characterization and to what extent M‐NVs components mimic exosomes remain elusive. M‐NVs were generated through the extrusion of cells and proteomic profiling demonstrated an enrichment of proteins associated with membrane and cytosolic components. The proteomic data herein reveal a subset of proteins that are highly abundant in M‐NVs in comparison to exosomes. M‐NVs contain proteins that largely represent the parental cell proteome, whereas the profile of exosomal proteins highlight their endosomally derived origin. This advantage of M‐NVs alleviates the necessity of endosomal sorting of endogenous therapeutic proteins or RNA into exosomes. This study also highlights differences in protein post‐translational modifications among M‐NVs, as distinct from exosomes. Overall this study provides key insights into defining the proteome composition of M‐NVs as a distinct from exosomes, and the potential advantage of M‐NVs as an alternative nanocarrier when spontaneous endosomal sorting of therapeutics are limited.

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Section: Resultssupporting

confidence: 82%

Proteomic and Post‐Translational Modification Profiling of Exosome‐Mimetic Nanovesicles Compared to Exosomes

et al. 2019

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“…Extrusion utilizes a lipid syringe extruder with pore sizes between 100 and 400 nm, which break the sEV membrane physically and then mix with therapeutics. This method possesses high loading efficiency when compared to freeze and thaw, sonication, and saponin treatment [ 155 , 157 ]. One can imagine that the extrusion approach may cause damage of the sEV membranes as it does by sonication and electroporation.…”

Section: Evs As Drug Carriers In Cancer Treatmentmentioning

confidence: 99%

“…It was demonstrated to be an effective approach for sEV encapsulation of therapeutic drugs when compared to electroporation [ 155 ]. While we would expect more studies using the transfection approach for sEV loading, especially for loading of nucleic acids, the chemical transfection reagent itself will need to be removed prior to delivering the sEVs to target cells [ 157 ].…”

Section: Evs As Drug Carriers In Cancer Treatmentmentioning

confidence: 99%

Extracellular Vesicles in the Development of Cancer Therapeutics

Sun

Burrola

et al. 2020

IJMS

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Extracellular vesicles (EVs) are small lipid bilayer-delimited nanoparticles released from all types of cells examined thus far. Several groups of EVs, including exosomes, microvesicles, and apoptotic bodies, have been identified according to their size and biogenesis. With extensive investigations on EVs over the last decade, it is now recognized that EVs play a pleiotropic role in various physiological processes as well as pathological conditions through mediating intercellular communication. Most notably, EVs have been shown to be involved in cancer initiation and progression and EV signaling in cancer are viewed as potential therapeutic targets. Furthermore, as membrane nanoparticles, EVs are natural products with some of them, such as tumor exosomes, possessing tumor homing propensity, thus leading to strategies utilizing EVs as drug carriers to effectively deliver cancer therapeutics. In this review, we summarize recent reports on exploring EVs signaling as potential therapeutic targets in cancer as well as on developing EVs as therapeutic delivery carriers for cancer therapy. Findings from preclinical studies are primarily discussed, with early phase clinical trials reviewed. We hope to provide readers updated information on the development of EVs as cancer therapeutic targets or therapeutic carriers.

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“…29,30 We also recently showed more than 100-fold production of ENVs compared to EVs from the same number of cells from mesenchymal stem cells and red blood cells. 31,32 Similarly, the ENVs can be produced from NIS-expressing cells on a large scale. In addition to our in vitro study, in vivo small animal studies are needed to evaluate efficiency of the EV-mediated transport of NIS protein.…”

Section: Discussionmentioning

confidence: 99%

<p>A novel strategy of transferring NIS protein to cells using extracellular vesicles leads to increase in iodine uptake and cytotoxicity</p>

Son¹,

Gangadaran²,

Ahn³

2019

IJN

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Background: This study was designed to explore a novel approach for transferring NIS protein to cells using extracellular vesicle (EV) and enhancing iodine avidity in hepatocellular carcinoma (HCC) cells. Methods: We transfected the HCC cells (Huh7) with NIS gene, designated as Huh7/NIS, and isolated the EVs from them. Presence of NIS protein in EVs and EV-mediated transport of NIS protein to recipient Huh7 cells were tested using Western blotting. We also examined radioiodine uptake in Huh7 cells treated with EV-Huh7/NIS. Results: Successful transfer of NIS protein into Huh7 cells was confirmed by WB and microscopy. EVs showed high levels of NIS protein in them. Treatment of Huh7 cells with EV-Huh7/ NIS increased the NIS protein level and enhanced 125 I uptake in recipient Huh7 cells. In addition, EV-huh7/NIS pre-treatment enhanced the cytotoxicity of 131 I therapy against Huh7 cells by inducing increased DNA damage/increased γH2A.X foci formation. Conclusion: This is the first-of-its-kind demonstration of successful transportation of the NIS protein to cells via EVs, which increased radioiodine uptake. This approach can revert radioiodine-resistant cancers into radioiodine-sensitive cancers.

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A New Approach for Loading Anticancer Drugs Into Mesenchymal Stem Cell-Derived Exosome Mimetics for Cancer Therapy

Cited by 206 publications

References 40 publications

Proteomic and Post‐Translational Modification Profiling of Exosome‐Mimetic Nanovesicles Compared to Exosomes

Proteomic and Post‐Translational Modification Profiling of Exosome‐Mimetic Nanovesicles Compared to Exosomes

Extracellular Vesicles in the Development of Cancer Therapeutics

<p>A novel strategy of transferring NIS protein to cells using extracellular vesicles leads to increase in iodine uptake and cytotoxicity</p>

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