A New Approach for Loading Anticancer Drugs Into Mesenchymal Stem Cell-Derived Exosome Mimetics for Cancer Therapy.
Senthilkumar Kalimuthu,Senthilkumar Kalimuthu,Prakash Gangadaran,Prakash Gangadaran,Ramya Lakshmi Rajendran,Ramya Lakshmi Rajendran,Liya Zhu,Liya Zhu,Ji Min Oh,Ji Min Oh,Ho-Won Lee,Ho-Won Lee,Arunnehru Gopal,Arunnehru Gopal,Se Hwan Baek,Se Hwan Baek,Shin Young Jeong,Shin Young Jeong,Sang-Woo Lee,Sang-Woo Lee,Jaetae Lee,Jaetae Lee,Byeong-Cheol Ahn,Byeong-Cheol Ahn +23 more
TLDR
MSC-EMs were successfully isolated using simple procedures and drug-loaded MSC- EMs were shown to be therapeutically efficient for the treatment of breast cancer both in vitro and in vivo.Abstract:
Exosomes derived from mesenchymal stem cells (MSCs) have been evaluated for their potential to be used as drug delivery vehicles. Synthetically personalized exosome mimetics (EMs) could be the alternative vesicles for drug delivery. In this study, we aimed to isolate EMs from human MSCs. Cells were mixed with paclitaxel (PTX) and PTX-loaded EMs (PTX-MSC-EMs) were isolated and evaluated for their anticancer effects against breast cancer. EMs were isolated from human bone marrow-derived MSCs. MSCs (4 × 106 cells/mL) were mixed with or without PTX at different concentrations in phosphate-buffered saline (PBS) and serially extruded through 10-, 5-, and 1-μm polycarbonate membrane filters using a mini-extruder. MSCs were centrifuged to remove debris and the supernatant was filtered through a 0.22-μm filter, followed by ultracentrifugation to isolate EMs and drug-loaded EMs. EMs without encapsulated drug (MSC-EMs) and those with encapsulated PTX (PTX-MSC-EMs) were characterized by western blotting, nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). The anticancer effects of MSC-EMs and PTX-MSC-EMs were assessed with breast cancer (MDA-MB-231) cells both in vitro and in vivo using optical imaging. EMs were isolated by the extrusion method and ultracentrifugation. The isolated vesicles were positive for membrane markers (ALIX and CD63) and negative for golgi (GM130) and endoplasmic (calnexin) marker proteins. NTA revealed the size of MSC-EM to be around 149 nm, while TEM confirmed its morphology. PTX-MSC-EMs significantly (p < 0.05) decreased the viability of MDA-MB-231 cells in vitro at increasing concentrations of EM. The in vivo tumor growth was significantly inhibited by PTX-MSC-EMs as compared to control and/or MSC-EMs. Thus, MSC-EMs were successfully isolated using simple procedures and drug-loaded MSC-EMs were shown to be therapeutically efficient for the treatment of breast cancer both in vitro and in vivo. MSC-EMs may be used as drug delivery vehicles for breast cancers.read more
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The emerging role of exosomes in mental disorders.
TL;DR: The roles of exosomes in the brain are discussed, novel findings are related to current insights into mental disorders, and novel findings from exosome studies derived from the brain may provide a mechanistic view of the disease phenotype.
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The role of exosomal noncoding RNAs in cancer
TL;DR: The role of exosomal ncRNAs, including miRNAs and long noncoding RNAs, in tumor biological processes is reviewed and may eventually become novel biomarkers and therapeutic targets in cancer progression.
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Bioinspired exosome-like therapeutics and delivery nanoplatforms.
Mei Lu,Yuanyu Huang +1 more
TL;DR: Efforts are made to give an overview of bioinspired exosome-like therapeutics and delivery nanoplatforms and to improve the loading capability and delivery efficiency of exosomes, hybrid exosom-like nanovesicles and membrane-camouflaged nanoparticles towards better bridging synthetic nanocarriers with naturalExosomes could be designed.
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Advances in Exosome-Based Drug Delivery and Tumor Targeting: From Tissue Distribution to Intracellular Fate.
TL;DR: This review summarizes recent advances in developing exosomes as drug delivery platforms with a focus on tumor targeting and highlights recently reported tumor-targeting strategies of exosome-based drug delivery in the hope that multiple approaches might be employed in a synergistic combination in the development of exo-based cancer therapy.
Journal ArticleDOI
The multifaceted role of mesenchymal stem cells in cancer.
TL;DR: The existing knowledge on the involvement of MSCs in multiple tumor-promoting processes, including angiogenesis, epithelial-mesenchymal transition, metastasis, immunosuppression and therapy resistance are reviewed.
References
More filters
Journal ArticleDOI
Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers
Johan Skog,T. Wurdinger,van Rijn S,Dimphna H. Meijer,Gainche L,Miguel Sena-Esteves,William T. Curry,Bob S. Carter,Anna M. Krichevsky,Xandra O. Breakefield +9 more
TL;DR: Tumour-derived microvesicles may provide diagnostic information and aid in therapeutic decisions for cancer patients through a blood test by incorporating an mRNA for a reporter protein into them, and it is demonstrated that messages delivered by microvesicle are translated by recipient cells.
Journal ArticleDOI
Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy.
TL;DR: This review offers a detailed description of different cytotoxic drug carriers, such as liposomes, carbon nanotubes, dendrimers, polymeric micelles,polymeric conjugates and polymeric nanoparticles, in passive and active targeted cancer therapy, by enhancing the permeability and retention or by the functionalization of the surface of the carriers.
Journal ArticleDOI
Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting
Oscar P. B. Wiklander,Joel Z. Nordin,Aisling J. O’Loughlin,Ylva Gustafsson,Giulia Corso,Imre Mäger,Pieter Vader,Yi Lee,Helena Sork,Yiqi Seow,Nina Heldring,Lydia Alvarez-Erviti,C. I. Edvard Smith,Katarina Le Blanc,Paolo Macchiarini,Philipp Jungebluth,Matthew J.A. Wood,Samir El Andaloussi +17 more
TL;DR: This is the first extensive biodistribution investigation of EVs comparing the impact of several different variables, the results of which have implications for the design and feasibility of therapeutic studies using EVs.
Journal ArticleDOI
Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma
Aarif Y. Khakoo,Aarif Y. Khakoo,Shibani Pati,Stasia A. Anderson,William Reid,Mohamed F. Elshal,Ilsa I Rovira,Ahn T Q Nguyen,Daniela Malide,Christian A. Combs,Gentzon Hall,Jianhu Zhang,Mark Raffeld,Terry B. Rogers,William G. Stetler-Stevenson,Joseph A. Frank,Marvin S. Reitz,Toren Finkel +17 more
TL;DR: The results suggest that in contrast to other stem cells or normal stromal cells, MSCs possess intrinsic antineoplastic properties and that this stem cell population might be of particular utility for treating those human malignancies characterized by dysregulated Akt.
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