OH but also employed as an oxidase to consume GSH, resulting in the amplification of chemotherapy and CDT.In addition, the fluorescent gold nanoclusters not only served as a peroxidase to convert H2O2 to Moreover, DOX could raise the level of H2O2 and augment the effect of CDT. The chemotherapeutic effect of DOX was strengthened through drug efflux inhibition and drug sensitivity increase due to the consumption of GSH and The Cu2+ ions could deplete the GSH via redox reactions and the generated Cu+ could convert internal H2O2 to
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The fluorescence signal of the tumor region was acquired after the quenched fluorescence of the gold nanoclusters by Cu2+ and DOX by aggregation-induced quenching was turned on because of the interaction of GSH with Cu2+ and the release of free DOX. The Cu2+-doped ZIF-8 shell was gradually degraded to release DOX and gold nanoclusters responding to the acidic TME. Herein, we reported the fabrication of copper ion-doped ZIF-8 loaded with gold nanozymes and doxorubicin hydrochloride (DOX) for the chemotherapy and CDT synergistic treatment of tumors with the assistance of tumor microenvironment (TME)-activated fluorescence imaging. OH scavenging by glutathione (GSH) and insufficient intratumoral H2O2 levels seriously hinder the application of CDT.
In summary, extrusion is a highly efficient method to generate a large quantity of therapeutic NVs that can potentially replace extracellular vesicles in regenerative medicine applications.Ĭhemodynamic therapy (CDT) is widely explored for tumor-specific therapy by converting endogenous H2O2 to lethal In addition, NV therapy promoted angiogenesis and proliferation of cardiomyocytes in the post-injury heart. Such therapeutic benefits are similar to those injected with natural EVs from the same MSC parental cells. Intramyocardial delivery of NVs in the injured heart after ischemia-reperfusion led to a reduction in scar sizes and preservation of cardiac functions. In vitro, cell-based assays demonstrated the myocardial protective effects and therapeutic potential of NVs. The yield of NVs is 20-fold more than that of EVs. Those extruded nanovesicles (NVs) are miniature versions of MSCs in terms of surface marker expression. We sought to develop a scale-up friendly method to generate a large number of therapeutic nanovesicles from MSCs by extrusion.
However, the large-scale production of EVs remains a challenge. The therapeutic potential of MSC-EVs has been established in various cardiac injury preclinical models. One of the important paracrine components of MSC secretomes is the extracellular vesicle (EV). Mesenchymal stem cells (MSCs) repair injured tissues mainly through their paracrine actions.
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