中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
Combination of irinotecan silicasome nanoparticles with radiation therapy sensitizes immunotherapy by modulating the activation of the cGAS/STING pathway for colorectal cancer

文献类型：期刊论文

作者Wang, Lu2,3; Zhang, Tianyu1,3; Zheng, Yile1,3; Li, Yuting3; Tang, Xiyuan2,3; Chen, Qianping2,3; Mao, Wei2,3; Li, Weiwei2,3; Liu, Xiangsheng2,3; Zhu, Ji2,3
刊名MATERIALS TODAY BIO
出版日期2023-12-01
卷号23页码:16
ISSN号2590-0064
DOI10.1016/j.mtbio.2023.100809
通讯作者Liu, Xiangsheng(xsliu@zju.edu.cn) ; Zhu, Ji(zhuji@zjcc.org.cn)
英文摘要Our previous clinical trial (Identifier: NCT02605265) revealed that addition of irinotecan (IRIN) to neoadjuvant chemoradiotherapy for rectal cancer could improve the curative effect. However, the adverse effects caused by IRIN limited the wide application of IRIN chemoradiotherapy. This study aimed to explore the mechanism under the synergistic effects of IRIN plus radiation therapy in colorectal cancer (CRC) cells and optimization of IRIN delivery via a silicasome nanocarrier in vivo. Our results revealed that compared with single IRIN or radiation treatment, IRIN combined with radiation therapy remarkably activated the intracellular cGAS/STING pathway, and promoted the expression levels of major histocompatibility complex class I (MHC-I) and programmed death ligand 1 (PD-L1). Further, a silicasome (mesoporous silica nanoparticle coated with lipid bilayer) nanocarrier was utilized to improve the delivery of IRIN with enhanced efficacy and reduced side effects. In the MC38 CRC syngeneic tumor model, IRIN silicasome combined with radiation therapy demonstrated a greater antitumor efficacy than free IRIN plus radiation therapy. Flow cytometry showed the increased number of CD4+ T cells, CD8+ T cells, and dendritic cells (DCs) in tumor in the IRIN silicasome plus radiation group. The immunofluorescence staining further confirmed the activated immune microenvironment with the elevated interferon-gamma (IFN-gamma) deposition. Besides, the anti-tumor effect of IRIN silicasome plus radiation therapy was synergistically enhanced by anti-PD-1 immunotherapy. These findings indicated that the combination of IRIN silicasome with radiation therapy could sensitize immunotherapy by manipulating the cGAS/STING pathway serving as a new strategy for CRC treatment.
WOS关键词RANDOMIZED PHASE-II ; RECTAL-CANCER ; NEOADJUVANT TREATMENT ; CAPECITABINE ; RADIOTHERAPY ; CHEMORADIATION ; TRIAL ; MULTICENTER ; OXALIPLATIN ; EFFICACY
资助项目Key Research Development Program of Zhejiang[2022C03015] ; National Natural Science Fund for Excellent Young Scientist Fund Program (Overseas) ; National Natural Science Foundation of China[32201143] ; Natural Science Foundation of Zhejiang[Q23H220007] ; National Health Commission Research Foundation[WKJ-ZJ-2305] ; CSCO Research Foundation[Y-NESTLE2022QN-0284]
WOS研究方向Engineering ; Materials Science
语种英语
出版者ELSEVIER
WOS记录号WOS:001097678000001
源URL[http://119.78.100.183/handle/2S10ELR8/307712]  
专题中国科学院上海药物研究所
通讯作者Liu, Xiangsheng; Zhu, Ji
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
2.Zhejiang Key Lab Radiat Oncol, Hangzhou 310022, Zhejiang, Peoples R China
3.Chinese Acad Sci, Zhejiang Canc Hosp, Hangzhou Inst Med HIM, Banshan Rd 1, Hangzhou 310022, Zhejiang, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Lu,Zhang, Tianyu,Zheng, Yile,et al. Combination of irinotecan silicasome nanoparticles with radiation therapy sensitizes immunotherapy by modulating the activation of the cGAS/STING pathway for colorectal cancer[J]. MATERIALS TODAY BIO,2023,23:16.
APA Wang, Lu.,Zhang, Tianyu.,Zheng, Yile.,Li, Yuting.,Tang, Xiyuan.,...&Zhu, Ji.(2023).Combination of irinotecan silicasome nanoparticles with radiation therapy sensitizes immunotherapy by modulating the activation of the cGAS/STING pathway for colorectal cancer.MATERIALS TODAY BIO,23,16.
MLA Wang, Lu,et al."Combination of irinotecan silicasome nanoparticles with radiation therapy sensitizes immunotherapy by modulating the activation of the cGAS/STING pathway for colorectal cancer".MATERIALS TODAY BIO 23(2023):16.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。