In Vivo Environment-Adaptive Nanocomplex with Tumor Cell-Specific Cytotoxicity Enhances T Cells Infiltration and Improves Cancer Therapy

doi:10.1002/smll.201902822

	In Vivo Environment-Adaptive Nanocomplex with Tumor Cell-Specific Cytotoxicity Enhances T Cells Infiltration and Improves Cancer Therapy
	Liu, Yiran 1,6,7; Lang, Tianqun 5,6,7; Zheng, Zhong 3,6,7; Cheng, Hui 4,6,7; Huang, Xin 5,6,7; Wang, Guanru 6,7; Yin, Qi 2,5,6,7; Li, Yaping 5,6,7
刊名	SMALL
	2019-10-01
卷号	15 期号:43 页码:12
关键词	breast cancer heparin sulfate metastasis nanocomplex T cells infiltration
ISSN号	1613-6810
DOI	10.1002/smll.201902822
通讯作者	Yin, Qi(qyin@simm.ac.cn) ; Li, Yaping(ypli@simm.ac.cn)
英文摘要	Drug delivery strategies possessing selectivity for cancer cells are eagerly needed in therapy of metastatic breast cancer. In this study, the chemotherapeutic agent, docetaxel (DTX), is conjugated onto heparan sulfate (HS). Aspirin (ASP), which has the activity of anti-metastasis and enhancing T cells infiltration in tumors, is encapsulated into the HS-DTX micelle. Then the cationic polyethyleneimine (PEI)-polyethylene glycol (PEG) copolymer binds to HS via electrostatic force, forming the ASP-loaded HS-DTX micelle (AHD)/PEI-PEG nanocomplex (PAHD). PAHD displays long circulation behavior in blood due to the PEG shell. Under the tumor microenvironment with weakly acidic pH, PEI-PEG separates from AHD, and the free cationic PEI-PEG facilitates the cellular uptake of AHD by increasing permeability of cell membranes. Then the overexpressed heparanase degrades HS, releasing ASP and DTX. PAHD shows specific toxicity toward tumor cells but not normal cells, with advanced activity of inhibiting tumor growth and lung metastasis in 4T1 tumor-bearing mice. The number of CD8(+) T cells in tumor tissues is also increased. Therefore, PAHD can become an efficient drug delivery system for breast cancer treatment.
WOS关键词	BREAST ; DELIVERY ; ASPIRIN ; NANOPARTICLES ; NANOMEDICINE ; MECHANISMS ; BLOCKADE ; GROWTH
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000491421600024
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/282736]
专题	中国科学院上海药物研究所
通讯作者	Yin, Qi; Li, Yaping
作者单位	1.Univ Sci & Technol China, Nano Sci & Technol Inst, Suzhou 215123, Peoples R China 2.Yantai Inst Materia Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Peoples R China 3.Jilin Univ, Coll Life Sci, Changchun 130012, Jilin, Peoples R China 4.Shenyang Pharmaceut Univ, Sch Pharm, Shenyang 110016, Liaoning, Peoples R China 5.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Materia Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China 7.Chinese Acad Sci, Shanghai Inst Materia Med, Ctr Pharmaceut, 501 Haike Rd, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Liu, Yiran,Lang, Tianqun,Zheng, Zhong,et al. In Vivo Environment-Adaptive Nanocomplex with Tumor Cell-Specific Cytotoxicity Enhances T Cells Infiltration and Improves Cancer Therapy[J]. SMALL,2019,15(43):12.
APA	Liu, Yiran.,Lang, Tianqun.,Zheng, Zhong.,Cheng, Hui.,Huang, Xin.,...&Li, Yaping.(2019).In Vivo Environment-Adaptive Nanocomplex with Tumor Cell-Specific Cytotoxicity Enhances T Cells Infiltration and Improves Cancer Therapy.SMALL,15(43),12.
MLA	Liu, Yiran,et al."In Vivo Environment-Adaptive Nanocomplex with Tumor Cell-Specific Cytotoxicity Enhances T Cells Infiltration and Improves Cancer Therapy".SMALL 15.43(2019):12.