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 l...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.展开更多
基金supported by National Natural Science Foundation of China(U190420008,31870994)。
文摘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.
