Inhibiting Endothelial Cell-Mediated T Lymphocyte Apoptosis with Integrin-Targeting Peptide-Drug Conjugate Filaments for Chemoimmunotherapy of Triple-Negative Breast Cancer

doi:10.1002/adma.202306676

	Inhibiting Endothelial Cell-Mediated T Lymphocyte Apoptosis with Integrin-Targeting Peptide-Drug Conjugate Filaments for Chemoimmunotherapy of Triple-Negative Breast Cancer
	Cai, Ying 1,2; Zhu, Binyu 1,2; Shan, Xiaoting 1,2; Zhou, Lingli 3; Sun, Xujie 1,2; Xia, Anqi 1,2; Wu, Binhao 1,2; Yu, Yang 4; Zhu, Helen He 5; Zhang, Pengcheng6 ; Li, Yaping 1,2,3,7,8
	2024-01-18
发表期刊	ADVANCED MATERIALS (IF:27.4[JCR-2023],30.2[5-Year])
ISSN	0935-9648
EISSN	1521-4095
卷号	36 期号:3
发表状态	已发表
DOI	10.1002/adma.202306676
摘要	Tumor-associated endothelial cells (TECs) limit antitumor immunity via inducing apoptosis of infiltrating T lymphocytes through a Fas ligand (FasL) mediated mechanism. Herein, this work creates a peptide-drug conjugate (PDC) by linking 7-ethyl-10-hydroxycamptothecin (SN38) to hydrophilic segments with either RGDR or HKD motif at their C-terminus through a glutathione-responsive linker. The PDCs spontaneously assemble into filaments in aqueous solution. The PDC filaments containing 1% of SN38-RGDR (SN38-HKD/RGDR) effectively target triple-negative breast cancer (TNBC) cells and TECs with upregulated expression of integrin, and induce immunogenic cell death (ICD) of tumor cells and FasL downregulation of TECs. SN38-HKD/RGDR increases infiltration, activity, and viability of CD8+ T cells, and thus inhibits the growth of primary tumors and pulmonary metastasis. This study highlights the synergistic modulation of cancerous cells and TECs with integrin-targeting PDC filaments as a promising strategy for TNBC chemoimmunotherapy. © 2023 Wiley-VCH GmbH.
关键词	Cell death Diseases Endothelial cells Ligands Peptides T-cells Drug-conjugates Endothelial-cells Fas ligand Immunotherapy Integrin targeting Peptide drugs Peptide-drug conjugate T lymphocytes Triple-negative breast cancers Tumor-associated endothelial cell
收录类别	EI
语种	英语
出版者	John Wiley and Sons Inc
EI入藏号	20234915151612
EI主题词	Tumors
EI分类号	461.2 Biological Materials and Tissue Engineering ; 461.9 Biology ; 461.9.1 Immunology ; 801.4 Physical Chemistry
原始文献类型	Article in Press
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/347922
专题	生物医学工程学院_PI研究组_张鹏程组
共同第一作者	Zhu, Binyu
通讯作者	Zhang, Pengcheng; Li, Yaping
作者单位	1.State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai; 201203, China; 2.University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing; 100049, China; 3.School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing; 210023, China; 4.National Facility for Protein Science in Shanghai, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai; 201210, China; 5.State Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Department of Urology, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai; 200127, China; 6.School of Biomedical Engineering & State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai; 201210, China; 7.Shandong Laboratory of Yantai Drug Discovery, Bohai rim Advanced Research Institute for Drug Discovery, Shandong; 264000, China; 8.Yantai Key Laboratory of Nanomedicine and Advanced Preparations, Yantai Institute of Pharmaceutical Science, Shandong; 264000, China
通讯作者单位	上海科技大学
推荐引用方式 GB/T 7714	Cai, Ying,Zhu, Binyu,Shan, Xiaoting,et al. Inhibiting Endothelial Cell-Mediated T Lymphocyte Apoptosis with Integrin-Targeting Peptide-Drug Conjugate Filaments for Chemoimmunotherapy of Triple-Negative Breast Cancer[J]. ADVANCED MATERIALS,2024,36(3).
APA	Cai, Ying.,Zhu, Binyu.,Shan, Xiaoting.,Zhou, Lingli.,Sun, Xujie.,...&Li, Yaping.(2024).Inhibiting Endothelial Cell-Mediated T Lymphocyte Apoptosis with Integrin-Targeting Peptide-Drug Conjugate Filaments for Chemoimmunotherapy of Triple-Negative Breast Cancer.ADVANCED MATERIALS,36(3).
MLA	Cai, Ying,et al."Inhibiting Endothelial Cell-Mediated T Lymphocyte Apoptosis with Integrin-Targeting Peptide-Drug Conjugate Filaments for Chemoimmunotherapy of Triple-Negative Breast Cancer".ADVANCED MATERIALS 36.3(2024).