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Brain-targeting biomimetic nanoparticles for codelivery of celastrol and LY2157299 for reversing glioma immunosuppression

文献类型：期刊论文

作者Zhu, Siqi4,5,6; Sun, Feifei5; Zhao, Pengfei5; Liang, Gang4,6; Sun, Xiaoyi6; Zeng, Linghui6; Huang, Yongzhuo1,2,3,5
刊名INTERNATIONAL JOURNAL OF PHARMACEUTICS
出版日期2022-05-10
卷号619页码:11
ISSN号0378-5173
关键词Glioblastoma Tumor-associated macrophages Brain-targeted delivery Celastrol Albumin nanoparticles
DOI10.1016/j.ijpharm.2022.121709
通讯作者Zeng, Linghui(zenglh@zucc.edu.cn) ; Huang, Yongzhuo(yzhuang@simm.ac.cn)
英文摘要The treatment of glioblastoma remains a huge challenge due to the lack of an efficient way to deliver drugs across the blood-brain barrier (BBB), and the pharmacotherapy options are very limited. In this work, a biomimetic BBB-penetrating albumin nanosystem modified by a brain-targeting peptide was designed for co-delivering a TGF-beta receptor I (TGF beta RI) inhibitor (LY2157299) and an mTOR inhibitor (celastrol). The albumin nanosystem can target nAChRs overexpressed both on the BBB and glioma cells, thereby promoting drug delivery into the glioma. The biomimetic nanoparticles could repolarize tumor-associated macrophages (TAMs) from M2 to M1 phenotype by suppressing the STAT6 pathway, thereby reducing TGF-beta 1 secretion and inducing cell apoptosis. In addition, the treatment also blocked TGF-beta/SMAD2 signaling pathway. The glioma-targeting ability and thera-peutic efficacy were confirmed in an orthotopic glioma mouse model. The biomimetic nanoparticles significantly prolonged the survival rate, showing a decrease in the proportion of M2-like TAMs and the levels of TGF-beta 1 and lactic acid in the glioma tissues. This delivery and treatment strategy provides a new approach for the treatment of gliomas.
WOS关键词MEDIATED TUMOR-GROWTH ; D-PEPTIDE LIGAND ; TGF-BETA ; CANCER ; CELLS ; MICROENVIRONMENT ; INHIBITION ; RESISTANCE ; THERAPY ; LACTATE
资助项目National Key Research and Development Program of China[2021YFE0103100] ; National Key Research and Development Program of China[2021YFC2400600] ; National Natural Science Foundation of China[NSFC 81925035] ; Shanghai Sci-Tech Innovation Initiative[19431903100] ; Shanghai Sci-Tech Innovation Initiative[18430740800] ; R&D Project of Zhejiang[20220C03034]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者ELSEVIER
WOS记录号WOS:000804783100002
源URL[http://119.78.100.183/handle/2S10ELR8/301364]  
专题新药研究国家重点实验室
通讯作者Zeng, Linghui; Huang, Yongzhuo
作者单位1.Taizhou Univ, Sch Adv Study, Inst Nat Med & Hlth Prod, Taizhou 318000, Peoples R China
2.NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipi, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, SIMM, Zhongshan 528437, Peoples R China
4.Zhejiang Univ, Dept Pharm, Hangzhou, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
6.Zhejiang Univ City Coll, Dept Pharmacol, 50 Huzhou Rd, Hangzhou 310015, Peoples R China
推荐引用方式
GB/T 7714		 Zhu, Siqi,Sun, Feifei,Zhao, Pengfei,et al. Brain-targeting biomimetic nanoparticles for codelivery of celastrol and LY2157299 for reversing glioma immunosuppression[J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS,2022,619:11.
APA Zhu, Siqi.,Sun, Feifei.,Zhao, Pengfei.,Liang, Gang.,Sun, Xiaoyi.,...&Huang, Yongzhuo.(2022).Brain-targeting biomimetic nanoparticles for codelivery of celastrol and LY2157299 for reversing glioma immunosuppression.INTERNATIONAL JOURNAL OF PHARMACEUTICS,619,11.
MLA Zhu, Siqi,et al."Brain-targeting biomimetic nanoparticles for codelivery of celastrol and LY2157299 for reversing glioma immunosuppression".INTERNATIONAL JOURNAL OF PHARMACEUTICS 619(2022):11.

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来源：上海药物研究所

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