Crystalline Mg-based alloys with a distinct reduction in hydrogen evolution were prepared through both electrochemical and microstructural engineering of the constituent phases. The addition of Zn to Mg-Ca alloy modified the corrosion potentials of two constituent phases (Mg + Mg2Ca), which prevented the formation of a galvanic circuit and achieved a comparable corrosion rate to high purity Mg. Furthermore, effective grain refinement induced by the extrusion allowed the achievement of much lower corrosion rate than high purity Mg. Animal studies confirmed the large reduction in hydrogen evolution and revealed good tissue compatibility with increased bone deposition around the newly developed Mg alloy implants. Thus, high strength Mg-Ca-Zn alloys with medically acceptable corrosion rate were developed and showed great potential for use in a new generation of biodegradable implants.
In this study, Cas9 system was employed to down-regulate mdr1 gene for overcoming multidrug resistance of cancer cells. Disruption of the MDR1 gene was achieved by delivery of the Cas9-sgRNA plasmid or the Cas9-sgRNA ribonucleoprotein complex using a conventional gene transfection agent and protein transduction domain (PTD). Doxorubicin showed considerable cytotoxicity to the drugresistant breast cancer cells pre-treated with the RNA-guided endonuclease (RGEN) systems, whereas virtually non-toxic to the untreated cells. The potency of drug was enhanced in the cells treated with the protein-RNA complex as well as in those treated with plasmids, suggesting that mutation of the mdr1 gene by intracellular delivery of Cas9-sgRNA complex using proper protein delivery platforms could recover the drug susceptibility. Therefore, Cas9-mediated disruption of the drug resistance-related gene can be considered as a promising way to overcome multidrug resistance in cancer cells.
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