Targeted combination therapy for glioblastoma by co-delivery of doxorubicin, YAP-siRNA and gold nano

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The combination of brain targeting drug delivery systems and multi-modal intervention pose a promising therapeutic approach for glioblastoma therapy.In this study,we developed an angiopep-2 peptide modified cationic liposome loaded with doxorubicin,YAP-siRNA and gold nanorods (D/R@Ang2-Lip + Au) simultaneously,which has high encapsulating efficiency for doxorubicin (95.4 %) and effective binding of siRNA at N/P ratio of 20∶1.The fluorescence imaging and flow cytometry analysis revealed high cellular uptake of D/R@Ang2-Lip + Au.Real-time quantitative polymerase chain reaction and western blot analysis indicated that D/R@Ang2-Lip + Au could effectively inhibit the expression of YAP protein.In vitro and in vivo studies showed that D/R@Ang2-Lip + Au had the ability to target glioblastoma cells,and achieved better anti-proliferative effects compared with non-targeted D/R@Lip + Au.Moreover,in vivo experiment demonstrated that D/R@Ang2-Lip + Au was able to cross the blood-brain barrier,and combination therapy could significantly inhibit tumor growth.Therefore,the multifunctional D/R@Ang2-Lip + Au might provide a novel approach for effectively delivery of DOX,YAP-siRNA and AuNRs into the glioblastoma cells simultaneously and exerting synergistic therapeutic effects.
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