文献类型：期刊文献

英文题名：Delivery of siRNA based on engineered exosomes for glioblastoma therapy by targeting STAT3

作者：Liang, Shi-Fu[1];Zuo, Fang-Fang[1];Yin, Bin-Cheng[1,2,3];Ye, Bang-Ce[1,2]

机构：[1]Zhejiang Univ Technol, Coll Pharmaceut Sci, Collaborat Innovat Ctr Yangtze River Delta Reg Gr, Hangzhou 310014, Zhejiang, Peoples R China;[2]East China Univ Sci & Technol, Lab Biosyst & Microanal, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[3]Shihezi Univ, Sch Chem & Chem Engn, Shihezi 832000, Xinjiang, Peoples R China

年份：2022

卷号：10

期号：6

起止页码：1582

外文期刊名：BIOMATERIALS SCIENCE

收录：;EI(收录号：20221411910850);WOS:【SCI-EXPANDED(收录号:WOS:000757517100001)】；

基金：This work was jointly supported by the National Key R&D Program of China (Grant 2020YFA0908800), the National Natural Science Foundation of China (Grants 21822402, 22134003), the "Shuguang Program" supported by the Shanghai Education Development Foundation and the Shanghai Municipal Education Commission, and the Natural Science Foundation of Zhejiang Province of China (Grant LHDMZ22H300008).

语种：英文

外文关键词：Disease control - Blood - RNA - Diagnosis

摘要：Small interfering RNA (siRNA) therapy has been considered as a promising strategy for treatment of glioblastoma (GBM), which is an aggressive brain disease with poor prognosis. However, siRNA therapy for GBM is seriously hindered by a multitude of barriers including possible immunogenicity, poor cellular uptake, short blood circulation, poor blood stability and low blood-brain barrier (BBB) penetration. This paper reports Angiopep-2 (An2)-functionalized signal transducers and activators of transcription 3 (STAT3) siRNA-loaded exosomes (Exo-An2-siRNA) as potential therapeutic agents to improve GBM therapy. The experimental results indicate that Exo-An2-siRNA displays high blood stability, efficient cellular uptake, and outstanding BBB penetration ability. Exo-An2-siRNA also exhibits excellent in vitro anti-GBM therapeutic effects due to the exosomes for siRNA protection and An2 modification for GBM targeting and BBB penetration. Such superior properties of Exo-An2-siRNA are responsible for favorable inhibition of the proliferation of orthotopic U87MG xenografts with limited side effects, significantly enhancing the median survival time (MST) of U87MG-bearing nude mice. The developed siRNA therapy featuring An2-functionalized exosomes as nanoplatforms is a safe and effective GBM treatment strategy.