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

Lihuang Li ¹Qiuyan Guo ¹Yanxiu Liu ²Mindan Lu ²Jun Yang ³Yunlong Ge ³Qiang Zhang ¹Benqiang Sun ⁴Xiumin Wang ²Li Liang-cheng ²Lei Ren⁵

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作者信息

1. Key Laboratory of Biomedical Engineering of Fujian Province University/Research Center of Biomedical Engineering of Xiamen, Department of Biomaterials, College of Materials, Xiamen University, Xiamen 361005, China
2. School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen 361102, China
3. Department of Neurosurgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361102, China
4. Stomatological Hospital of Xiamen Medical College, Xiamen 361105, China
5. Key Laboratory of Biomedical Engineering of Fujian Province University/Research Center of Biomedical Engineering of Xiamen, Department of Biomaterials, College of Materials, Xiamen University, Xiamen 361005, China;State Key Lab of Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen 361005, China
折叠

Abstract

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.

Key words

Cationic liposomes/Angiopep-2/Doxorubicin/YAP siRNA/AuNRs/Glioblastoma treatment

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基金项目

出版年

2021

材料科学技术(英文版)

中国金属学会中国材料研究学会中国科学院金属研究所

材料科学技术(英文版)

CSTPCDCSCDSCI

影响因子：0.657

ISSN：1005-0302

参考文献量39

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