A DNA/DMXAA/Metal-Organic Framework Activator of Innate Immunity for Boosting Anticancer Immunity

被引:58
作者
Chen, Xiaojing [1 ,2 ]
Tang, Qianyun [1 ]
Wang, Jinqiang [3 ]
Zhou, Yan [1 ,2 ]
Li, Fengqin [1 ]
Xie, Yuexia [1 ,2 ]
Wang, Xingang [1 ]
Du, Ling [1 ]
Li, Junru [1 ]
Pu, Jun [1 ]
Hu, Quanyin [4 ]
Gu, Zhen [3 ]
Liu, Peifeng [1 ,2 ]
机构
[1] Shanghai Jiao Tong Univ, Ren Ji Hosp, Shanghai Canc Inst, Sch Med,State Key Lab Oncognes & Related Genes, Shanghai 200032, Peoples R China
[2] Shanghai Jiao Tong Univ, Ren Ji Hosp, Sch Med, Cent Lab, Shanghai 200127, Peoples R China
[3] Zhejiang Univ, Coll Pharmaceut Sci, Key Lab Adv Drug Delivery Syst Zhejiang Prov, Hangzhou 310058, Peoples R China
[4] Univ Wisconsin Madison, Sch Pharm, Pharmaceut Sci Div, Madison, WI 53705 USA
基金
中国国家自然科学基金; 国家重点研发计划;
关键词
DNA; drug delivery; immunotherapy; metal-organic frameworks; stimulator of interferon genes agonist; DENDRITIC CELLS; BACTERIAL-DNA; ADSORPTION; CANCER; ANGIOGENESIS;
D O I
10.1002/adma.202210440
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Immunotherapy has achieved revolutionary success in clinics, but it remains challenging for treating hepatocellular carcinoma (HCC) characterized by high vascularization. Here, it is reported that metal-organic framework-801 (MOF-801) can be employed as a stimulator of interferon genes (STING) through Toll-like receptor 4 (TLR4) not just as a drug delivery carrier. Notably, cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) and 5, 6-dimethylxanthenone-4-acetic acid (DMXAA) STING agonist with vascular disrupting function coordinates with MOF-801 to self-assemble into a nanoparticle (MOF-CpG-DMXAA) that effectively delivers CpG ODNs and DMXAA to cells for synergistically improving the tumor microenvironment by reprogramming tumor-associated macrophages (TAMs), promoting dendritic cells (DCs) maturation, as well as destroying tumor blood vessels. In HCC-bearing mouse models, it is demonstrated that MOF-CpG-DMXAA triggers systemic immune activation and stimulates robust tumoricidal immunity, resulting in a superior immunotherapeutic efficiency in orthotopic and recurrent HCC.
引用
收藏
页数:14
相关论文
共 47 条
[1]   Toll-like receptor agonists induce apoptosis in mouse B-cell lymphoma cells by altering NF-κB activation [J].
Arunkumar, Nandini ;
Liu, Chaohong ;
Hang, Haiying ;
Song, Wenxia .
CELLULAR & MOLECULAR IMMUNOLOGY, 2013, 10 (04) :360-372
[2]   Divergent therapeutic and immunologic effects of oligodeoxynucleotides with distinct CpG motifs [J].
Ballas, ZK ;
Krieg, AM ;
Warren, T ;
Rasmussen, W ;
Davis, HL ;
Waldschmidt, M ;
Weiner, GJ .
JOURNAL OF IMMUNOLOGY, 2001, 167 (09) :4878-4886
[3]   Chronic innate immune activation as a cause of HIV-1 immunopathogenesis [J].
Boasso, Adriano ;
Shearer, Gene M. .
CLINICAL IMMUNOLOGY, 2008, 126 (03) :235-242
[4]   Self-Assembly of Poly-Adenine-Tailed CpG Oligonucleotide-Gold Nanoparticle Nanoconjugates with Immunostimulatory Activity [J].
Chen, Nan ;
Wei, Min ;
Sun, Yanhong ;
Li, Fan ;
Pei, Hao ;
Li, Xiaoming ;
Su, Shao ;
He, Yao ;
Wang, Lianhui ;
Shi, Jiye ;
Fan, Chunhai ;
Huang, Qing .
SMALL, 2014, 10 (02) :368-375
[5]   STING Pathway Activation Stimulates Potent Immunity against Acute Myeloid Leukemia [J].
Curran, Emily ;
Chen, Xiufen ;
Corrales, Leticia ;
Kline, Douglas E. ;
Dubensky, Thomas W., Jr. ;
Duttagupta, Priyanka ;
Kortylewski, Marcin ;
Kline, Justin .
CELL REPORTS, 2016, 15 (11) :2357-2366
[6]   Mitochondria Targeted Nanoscale Zeolitic Imidazole Framework-90 for ATP Imaging in Live Cells [J].
Deng, Jingjing ;
Wang, Kai ;
Wang, Ming ;
Yu, Ping ;
Mao, Lanqun .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2017, 139 (16) :5877-5882
[7]   M2 macrophage-induced lncRNA PCAT6 facilitates tumorigenesis and angiogenesis of triple-negative breast cancer through modulation of VEGFR2 [J].
Dong, Fang ;
Ruan, Shengnan ;
Wang, Jinlong ;
Xia, Yun ;
Le, Kehao ;
Xiao, Xiaoyun ;
Hu, Ting ;
Wang, Qiong .
CELL DEATH & DISEASE, 2020, 11 (09)
[8]   DMXAA Causes Tumor Site-Specific Vascular Disruption in Murine Non-Small Cell Lung Cancer, and like the Endogenous Non-Canonical Cyclic Dinucleotide STING Agonist, 2′3′-cGAMP, Induces M2 Macrophage Repolarization [J].
Downey, Charlene M. ;
Aghaei, Mehrnoosh ;
Schwendener, Reto A. ;
Jirik, Frank R. .
PLOS ONE, 2014, 9 (06)
[9]   Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial [J].
El-Khoueiry, Anthony B. ;
Sangro, Bruno ;
Yau, Thomas ;
Crocenzi, Todd S. ;
Kudo, Masatoshi ;
Hsu, Chiun ;
Kim, Tae-You ;
Choo, Su-Pin ;
Trojan, Jorg ;
Welling, Theodore H., III ;
Meyer, Tim ;
Kang, Yoon-Koo ;
Yeo, Winnie ;
Chopra, Akhil ;
Anderson, Jeffrey ;
dela Cruz, Christine ;
Lang, Lixin ;
Neely, Jaclyn ;
Tang, Hao ;
Dastani, Homa B. ;
Melero, Ignacio .
LANCET, 2017, 389 (10088) :2492-2502
[10]   Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma [J].
Finn, Richard S. ;
Qin, Shukui ;
Ikeda, Masafumi ;
Galle, Peter R. ;
Ducreux, Michel ;
Kim, Tae-You ;
Kudo, Masatoshi ;
Breder, Valeriy ;
Merle, Philippe ;
Kaseb, Ahmed O. ;
Li, Daneng ;
Verret, Wendy ;
Xu, Derek-Zhen ;
Hernandez, Sairy ;
Liu, Juan ;
Huang, Chen ;
Mulla, Sohail ;
Wang, Yulei ;
Lim, Ho Yeong ;
Zhu, Andrew X. ;
Cheng, Ann-Lii .
NEW ENGLAND JOURNAL OF MEDICINE, 2020, 382 (20) :1894-1905