期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 144, 期 2, 页码 787-797出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.1c09753
关键词
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资金
- National Natural Science Foundation of China (NSFC) [32171318, 32101069]
- Faculty of Health Sciences, University of Macau
- University of Macau [SRG2018-00130-FHS]
- Science and Technology Development Fund, Macau SAR [0109/2018/A3, 0011/2019/AKP, 0113/2019/A2, 0103/2021/A]
- Shenzhen Science and Technology Innovation Commission, Shenzhen-Hong Kong-Macau Science and Technology Plan C [SGDX20201103093600004]
- Proteomics, Metabolomics and Drug Development Core in the Faculty of Health Sciences, University of Macau
- Animal Research Core in the Faculty of Health Sciences, University of Macau
- Biological Imaging and Stem Cell Core in the Faculty of Health Sciences, University of Macau
In this study, phototheranostic metal-phenolic networks were engineered for precise photo thermal therapy. This therapy could relieve exosomal suppression, restore T cells, and enhance ferroptosis. The synergy of photo thermal therapy with antiexosomal PD-L1 evoked potent antitumor immunity and immunological memory against metastatic tumors.
Tumor-derived exosome can suppress dendritic cells (DCs) and T cells functions. Excessive secretion of exosomal programmed death-ligand 1 (PD-L1) results in therapeutic resistance to PD-1/PD-L1 immunotherapy and clinical failure. Restored T cells by antiexosomal PD-Ll tactic can intensify ferroptosis of tumor cells and vice versa. Diminishing exosomal suppression and establishing a nexus of antiexosomal PD-L1 and ferroptosis may rescue the discouraging antitumor immunity. Here, we engineered phototheranostic metal-phenolic networks (PFG MPNs) by an assembly of semiconductor polymers encapsulating ferroptosis inducer (Fe3+) and exosome inhibitor (GW4869). The PFG MPNs elicited superior near-infrared II fluorescence/photoacoustic imaging tracking performance for a precise photo thermal therapy (PTT). PTT-augmented immunogenic cell death relieved exosomal silencing on DC maturation. GW4869 mediated PD-L1 based exosomal inhibition revitalized T cells and enhanced the ferroptosis. This novel synergy of PTT with antiexosomal PD-L1 enhanced ferroptosis evoked potent antitumor immunity in B16F10 tumors and immunological memory against metastatic tumors in lymph nodes.
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