Abstract:Exosomes are physiologically secreted nanoparticles recently established as natural delivery systems involved in cell-to-cell communication and content exchange. Due to their inherent targeting potential, exosomes are currently being harnessed for the development of anti-cancer therapeutics. Clinical trials evaluating their effectiveness are demonstrating safety and promising outcomes. However, challenging largescale production, isolation, modification and purification of exosomes are current limitations for t… Show more
“…Fortunately, research on the production of exosome mimics has made preliminary progress. Pisano et al (201) used monocytes as raw materials to produce exosome mimics through filters of different porosity and size exclusion chromatography columns. The development of immune-derived exosome mimics is expected to solve the problems of yield and reproducibility, which greatly improves the feasibility of applying exosomes to clinical trials (201).…”
Exosomes are excretory vesicles that can deliver a variety of bioactive cargo molecules to the extracellular environment. Accumulating evidence demonstrates exosome participation in intercellular communication, immune response, inflammatory response and they even play an essential role in affecting the tumor immune microenvironment. The role of exosomes in the immune microenvironment of ovarian cancer is mainly divided into suppression and stimulation. On one hand exosomes can stimulate the innate and adaptive immune systems by activating dendritic cells (DCs), natural killer cells and T cells, allowing these immune cells exert an antitumorigenic effect. On the other hand, ovarian cancer-derived exosomes initiate cross-talk with immunosuppressive effector cells, which subsequently cause immune evasion; one of the hallmarks of cancer. Exosomes induce the polarization of macrophages in M2 phenotype and induce apoptosis of lymphocytes and DCs. Exosomes further activate additional immunosuppressive effector cells (myeloid-derived suppressor cells and regulatory T cells) that induce fibroblasts to differentiate into cancer-associated fibroblasts. Exosomes also induce the tumorigenicity of mesenchymal stem cells to exert additional immune suppression. Furthermore, besides mediating the intercellular communication, exosomes carry microRNAs (miRNAs), proteins and lipids to the tumor microenvironment, which collectively promotes ovarian cancer cells to proliferate, invade and tumors to metastasize. Studying proteins, lipids and miRNAs carried by exosomes could potentially be used as an early diagnostic marker of ovarian cancer for designing treatment strategies.
“…Fortunately, research on the production of exosome mimics has made preliminary progress. Pisano et al (201) used monocytes as raw materials to produce exosome mimics through filters of different porosity and size exclusion chromatography columns. The development of immune-derived exosome mimics is expected to solve the problems of yield and reproducibility, which greatly improves the feasibility of applying exosomes to clinical trials (201).…”
Exosomes are excretory vesicles that can deliver a variety of bioactive cargo molecules to the extracellular environment. Accumulating evidence demonstrates exosome participation in intercellular communication, immune response, inflammatory response and they even play an essential role in affecting the tumor immune microenvironment. The role of exosomes in the immune microenvironment of ovarian cancer is mainly divided into suppression and stimulation. On one hand exosomes can stimulate the innate and adaptive immune systems by activating dendritic cells (DCs), natural killer cells and T cells, allowing these immune cells exert an antitumorigenic effect. On the other hand, ovarian cancer-derived exosomes initiate cross-talk with immunosuppressive effector cells, which subsequently cause immune evasion; one of the hallmarks of cancer. Exosomes induce the polarization of macrophages in M2 phenotype and induce apoptosis of lymphocytes and DCs. Exosomes further activate additional immunosuppressive effector cells (myeloid-derived suppressor cells and regulatory T cells) that induce fibroblasts to differentiate into cancer-associated fibroblasts. Exosomes also induce the tumorigenicity of mesenchymal stem cells to exert additional immune suppression. Furthermore, besides mediating the intercellular communication, exosomes carry microRNAs (miRNAs), proteins and lipids to the tumor microenvironment, which collectively promotes ovarian cancer cells to proliferate, invade and tumors to metastasize. Studying proteins, lipids and miRNAs carried by exosomes could potentially be used as an early diagnostic marker of ovarian cancer for designing treatment strategies.
“…This biomimetic system showed the potential to revolutionize the treatment of cancers due to stable drug delivery with reduced immunogenicity. 256 A similar study was conducted by Kalimuthu et al in 2018, demonstrating an alternative to paclitaxel (PTX) drug delivery by synthetically prepared exosomemimetics (EMs). To isolate EMs, human mesenchymal stem cells (MSCs) were treated with PTX and serially extruded using polycarbonate membrane filters in a miniextruder similar to the previously discussed example.…”
Section: Perspective On Innovative Systems Utilizing Exosomes For Drug Deliverymentioning
confidence: 78%
“…This biomimetic system showed the potential to revolutionize the treatment of cancers due to stable drug delivery with reduced immunogenicity. 256 Figure 15 ( A ) Characterization of EXO and IDEM. I) Size (nm) and concentration (particles/mL) as per NTA, II) the number of CD63 positive EXO and IDEM obtained from ELISA (* P < 0.05), III) positive signal in flow cytometry for APC-CD81 antibody stained EXO and IDEM, IV) particle morphology revealed from scanning electron microscopy, V) presence of tsg-101 marker obtained from Western blotting.…”
Section: Perspective On Innovative Systems Utilizing Exosomes For Drug Deliverymentioning
The increasing incidence of bone-related disorders is causing a burden on the clinical scenario. Even though bone is one of the tissues that possess tremendous regenerative potential, certain bone anomalies need therapeutic intervention through appropriate delivery of a drug. Among several nanosystems and biologics that offer the potential to contribute towards bone healing, the exosomes from the class of extracellular vesicles are outstanding. Exosomes are extracellular nanovesicles that, apart from the various advantages, are standing out of the crowd for their ability to conduct cellular communication. The internal cargo of the exosomes is leading to its potential use in therapeutics. Exosomes are being unraveled in terms of the mechanism as well as application in targeting various diseases and tissues. Through this review, we have tried to understand and review all that is already established and the gap areas that still exist in utilizing them as drug delivery vehicles targeting the bone. The review highlights the potential of the exosomes towards their contribution to the drug delivery scenario in the bone microenvironment. A comparison of the pros and cons of exosomes with other prevalent drug delivery systems is also done. A section on the patents that have been generated so far from this field is included.
“…When loaded with doxorubicin, these EVs mimetics were more effective in targeting ovarian cancer cells in 3D cultures than free doxorubicin. In addition, they showed a higher encapsulation efficiency and drug release over time in comparison to naturally released EVs [ 84 ]. Spheroids derived from cancer stem cell have been targeted with tumor-cell-exocytosed nanoparticles made of porous silicon.…”
Section: Modelling the Antitumoral Effect Of Evs In 3d Culturesmentioning
The improvement of culturing techniques to model the environment and physiological conditions surrounding tumors has also been applied to the study of extracellular vesicles (EVs) in cancer research. EVs role is not only limited to cell-to-cell communication in tumor physiology, they are also a promising source of biomarkers, and a tool to deliver drugs and induce antitumoral activity. In the present review, we have addressed the improvements achieved by using 3D culture models to evaluate the role of EVs in tumor progression and the potential applications of EVs in diagnostics and therapeutics. The most employed assays are gel-based spheroids, often utilized to examine the cell invasion rate and angiogenesis markers upon EVs treatment. To study EVs as drug carriers, a more complex multicellular cultures and organoids from cancer stem cell populations have been developed. Such strategies provide a closer response to in vivo physiology observed responses. They are also the best models to understand the complex interactions between different populations of cells and the extracellular matrix, in which tumor-derived EVs modify epithelial or mesenchymal cells to become protumor agents. Finally, the growth of cells in 3D bioreactor-like systems is appointed as the best approach to industrial EVs production, a necessary step toward clinical translation of EVs-based therapy.
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