A Three-In-One Assembled Nanoparticle Containing Peptide–Radio-Sensitizer Conjugate and TLR7/8 Agonist Can Initiate the Cancer-Immunity Cycle to Trigger Antitumor Immune Response
Xueqin Zhu
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorXiaoxi Wang
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorBingyu Li
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorYun Zhang
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorYalan Chen
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorWenyan Zhang
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorYan Wang
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorWenjie Zhai
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Henan Key Laboratory of Bioactive Macromolecules, Zhengzhou University, Zhengzhou, 450001 China
International Joint Laboratory for Protein and Peptide Drugs of Henan Province, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorZimai Liu
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorSijia Liu
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorJiaxin Sun
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorCorresponding Author
Zhenzhen Chen
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Henan Key Laboratory of Bioactive Macromolecules, Zhengzhou University, Zhengzhou, 450001 China
International Joint Laboratory for Protein and Peptide Drugs of Henan Province, Zhengzhou University, Zhengzhou, 450001 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Yanfeng Gao
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorXueqin Zhu
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorXiaoxi Wang
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorBingyu Li
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorYun Zhang
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorYalan Chen
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorWenyan Zhang
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorYan Wang
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorWenjie Zhai
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Henan Key Laboratory of Bioactive Macromolecules, Zhengzhou University, Zhengzhou, 450001 China
International Joint Laboratory for Protein and Peptide Drugs of Henan Province, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorZimai Liu
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorSijia Liu
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorJiaxin Sun
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Search for more papers by this authorCorresponding Author
Zhenzhen Chen
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
Henan Key Laboratory of Bioactive Macromolecules, Zhengzhou University, Zhengzhou, 450001 China
International Joint Laboratory for Protein and Peptide Drugs of Henan Province, Zhengzhou University, Zhengzhou, 450001 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Yanfeng Gao
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001 China
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorAbstract
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 DPPA-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.
Conflict of Interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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| smll202107001-sup-0001-SuppMat.pdf1.5 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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