免疫系统
TLR7型
癌细胞
癌症研究
结合
细胞凋亡
癌症
化学
细胞生物学
免疫学
医学
先天免疫系统
生物
生物化学
Toll样受体
内科学
数学分析
数学
作者
Xueqin Zhu,Xiaoxi Wang,Bingyu Li,Yun Zhang,Yalan Chen,Wenyan Zhang,Yan Wang,Wenjie Zhai,Zimai Liu,Sijia Liu,Jiaxin Sun,Zhenzhen Chen,Yanfeng Gao
出处
期刊:Small
[Wiley]
日期:2022-04-17
卷期号:18 (20)
被引量:27
标识
DOI:10.1002/smll.202107001
摘要
Abstract Radiotherapy (RT) has been shown to cause immunogenic cell death (ICD) of cancer cells, which promote the release of tumor‐associated antigens, and trigger the cancer‐immunity cycle (CIC). However, ICD induced by RT usually does not occur in hypoxic tumor cells due to their resistance to radiation. Moreover, RT also induces programmed death ligand 1 (PD‐L1) upregulation on tumor cells, which has an inhibitory effect on T lymphocytes. Therefore, therapy based on CIC must selectively target the restricted steps of antitumor immunity. Herein, the authors design a versatile three‐in‐one assembling nanoparticle that can simultaneously execute these obstacles. The amphiphilic peptide drug conjugate NIA‐D1, containing the hydrophobic radio‐sensitizer 2‐(2‐nitroimidazol‐1‐yl) acetic acid (NIA), a peptide substrate of matrix metalloproteinase‐2, and a hydrophilic PD‐L1 antagonist D PPA‐1, is constructed and co‐assembled with hydrophobic Toll‐like receptor (TLR) 7/8 agonist R848 to form nanoparticle NIA‐D1@R848. The NIA‐D1@R848 nanoparticles combined with RT can trigger the apoptosis of tumor cells and initiate the CIC. In the presence of R848, it promotes the maturation of dendritic cells, which together with protein programmed cell death protein 1 (PD‐1) and its ligand PD‐L1 blockade to relieve T cell suppression, and amplify the antitumor immune cycle. In conclusion, a functionalized three‐in‐one nanoparticle NIA‐D1@R848 is successfully constructed, which can induce strong systemic antitumor immune response.
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