Biomimetic codelivery overcomes osimertinib-resistant NSCLC and brain metastasis via macrophage-mediated innate immunity

doi:10.1016/j.jconrel.2020.10.052

	Biomimetic codelivery overcomes osimertinib-resistant NSCLC and brain metastasis via macrophage-mediated innate immunity
	Zhao, Pengfei 1,2; Zhang, Jiaxin 2; Wu, Aihua 3; Zhang, Meng 2; Zhao, Yuge 2,4; Tang, Yisi 2; Wang, Bing 2; Chen, Tianxiang 5; Li, Feng 6; Zhao, Qiang 2
刊名	JOURNAL OF CONTROLLED RELEASE
	2021-01-10
卷号	329 页码:1249-1261
关键词	Brain targeting delivery Tumor-associated macrophage Osimertinib resistance Brain metastasis Innate immunity Combination therapy
ISSN号	0168-3659
DOI	10.1016/j.jconrel.2020.10.052
通讯作者	Zhao, Qiang(zhaoq@simm.ac.cn) ; Huang, Yongzhuo(yzhuang@simm.ac.cn)
英文摘要	The third-generation of EGFR-TKI osimertinib has been approved as a first-line therapy in NSCLC, representing the most successful advance in molecularly targeted therapy. However, the rapid development of osimertinib resistance renders the unsustainable treatment benefit. Plus, brain metastasis (BMs) is a major mortality cause for NSCLC; there is no drug specifically approved for the osimertinib-resistant BMs of NSCLC yet. To tackle these critical issues, a BBB-permeable biomimetic codelivery system was designed for specifically treating osimertinib-resistant BMs. The T12 peptide-modified albumin nanoparticles coloaded with regorafenib and disulfiram/copper ion chelate repolarized the tumor-promoting CD206(hi) TGF-beta 1(+) M Phi via inhibition of FROUNT and thus remodeled tumor immune microenvironment. The treatment efficacy in both the subcutaneous H1975/AZDR model and the brain metastasized model demonstrated the effectiveness of the BBB-penetrating combination therapy and the macrophage-mediated innate immunity. This nanotherapeutic combination strategy provides a translational solution to the formidable challenges of overcoming TKI resistance and treating the TKI-resistant BMs.
资助项目	NFSC[81925035] ; NFSC[81673382] ; NFSC[81521005] ; Strategic Priority Research Program of CAS[XDA12050307] ; National Special Project for Significant New Drugs Development[2018ZX09711002-010-002] ; Shanghai SciTech Innovation Initiative[19431903100] ; Shanghai SciTech Innovation Initiative[18430740800] ; Shanghai Collaborative Innovation Group of Early Diagnosis and Precise Treatment of Hemangiomas and Vascular Malformations[SSMUZDCX20180701]
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER
WOS记录号	WOS:000626334700092
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/295233]
专题	中国科学院上海药物研究所
通讯作者	Zhao, Qiang; Huang, Yongzhuo
作者单位	1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, 138 Xianlin Ave, Nanjing 210023, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China 3.Fudan Univ, Sch Pharm, Key Lab Smart Drug Delivery, Minist Educ, 826 Zhangheng Rd, Shanghai 201203, Peoples R China 4.Nanchang Univ, Coll Pharm, 461 Bayi Rd, Nanchang 330006, Jiangxi, Peoples R China 5.Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Shanghai 200030, Peoples R China 6.Auburn Univ, Harrison Sch Pharm, Auburn, AL 36849 USA 7.NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipi, Shanghai 201203, Peoples R China 8.Chinese Acad Sci, Inst Drug Res & Dev, Zhongshan Branch, Zhongshan 528437, Peoples R China
推荐引用方式 GB/T 7714	Zhao, Pengfei,Zhang, Jiaxin,Wu, Aihua,et al. Biomimetic codelivery overcomes osimertinib-resistant NSCLC and brain metastasis via macrophage-mediated innate immunity[J]. JOURNAL OF CONTROLLED RELEASE,2021,329:1249-1261.
APA	Zhao, Pengfei.,Zhang, Jiaxin.,Wu, Aihua.,Zhang, Meng.,Zhao, Yuge.,...&Huang, Yongzhuo.(2021).Biomimetic codelivery overcomes osimertinib-resistant NSCLC and brain metastasis via macrophage-mediated innate immunity.JOURNAL OF CONTROLLED RELEASE,329,1249-1261.
MLA	Zhao, Pengfei,et al."Biomimetic codelivery overcomes osimertinib-resistant NSCLC and brain metastasis via macrophage-mediated innate immunity".JOURNAL OF CONTROLLED RELEASE 329(2021):1249-1261.