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
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出版日期 | 2023-12-01 |
卷号 | 23页码:16 |
ISSN号 | 2590-0064 |
DOI | 10.1016/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 |
WOS记录号 | WOS:001097678000001 |
出版者 | ELSEVIER |
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
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