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A BRD4 PROTAC nanodrug for glioma therapy via the intervention of tumor cells proliferation, apoptosis and M2 macrophages polarization.

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Pubmed体系：

收录情况： ◇ 统计源期刊 ◇ CSCD-C ◇ 卓越：领军期刊

作者：
Yang Tingting[1] * ; Hu Yuzhu[1,2] * ; Miao Junming[1] * ; Chen Jing[1] ; Liu Jiagang[1] ; Cheng Yongzhong[1] ; Gao Xiang[1] ;
机构： [1]Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China [2]Department of Medical Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
出处：
DOI： 10.1016/j.apsb.2022.02.009
ISSN：

关键词： Glioma BRD4 ARV-825 Micelle M2 macrophage

摘要：
Glioma is a primary aggressive brain tumor with high recurrence rate. The poor efficiency of chemotherapeutic drugs crossing the blood‒brain barrier (BBB) is well-known as one of the main challenges for anti-glioma therapy. Moreover, massive infiltrated tumor-associated macrophages (TAMs) in glioma further thwart the drug efficacy. Herein, a therapeutic nanosystem (SPP-ARV-825) is constructed by incorporating the BRD4-degrading proteolytic targeting chimera (PROTAC) ARV-825 into the complex micelle (SPP) composed of substance P (SP) peptide-modified poly(ethylene glycol)-poly(d,l-lactic acid)(SP-PEG-PDLLA) and methoxy poly(ethylene glycol)-poly(d,l-lactic acid) (mPEG-PDLLA, PP), which could penetrate BBB and target brain tumor. Subsequently, released drug engenders antitumor effect via attenuating cells proliferation, inducing cells apoptosis and suppressing M2 macrophages polarization through the inhibition of IRF4 promoter transcription and phosphorylation of STAT6, STAT3 and AKT. Taken together, our work demonstrates the versatile role and therapeutic efficacy of SPP-ARV-825 micelle against glioma, which may provide a novel strategy for glioma therapy in future.© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

基金：
NationalNatural Science Foundation of China (No. 82172630, 81972347 and 82003493), the Key R&D Projects of the Science and Technology Department of Sichuan Province (No. 2020YFS0213, China) and the 1$3$5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (No. ZYJC21022, No. ZYYC21001 and 2019HXFH017, China).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 化学
小类 | 1 区 药学
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 药学
第一作者：
第一作者机构： [1]Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Yang Tingting,Hu Yuzhu,Miao Junming,et al.A BRD4 PROTAC nanodrug for glioma therapy via the intervention of tumor cells proliferation, apoptosis and M2 macrophages polarization.[J].Acta Pharmaceutica Sinica B.2022,12(6):2658-2671.doi:10.1016/j.apsb.2022.02.009.
APA：
Yang Tingting,Hu Yuzhu,Miao Junming,Chen Jing,Liu Jiagang...&Gao Xiang.(2022).A BRD4 PROTAC nanodrug for glioma therapy via the intervention of tumor cells proliferation, apoptosis and M2 macrophages polarization..Acta Pharmaceutica Sinica B,12,(6)
MLA：
Yang Tingting,et al."A BRD4 PROTAC nanodrug for glioma therapy via the intervention of tumor cells proliferation, apoptosis and M2 macrophages polarization.".Acta Pharmaceutica Sinica B 12..6(2022):2658-2671

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