期刊
BIOMATERIALS
卷 269, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2020.120638
关键词
Phenolic nanoplatform; Metal phenolic coordination; Immunogenic cell death; PD-1 immune checkpoint blockade immunotherapy
资金
- Faculty of Health Sciences, University of Macau
- Startup Research Grant (SRG) of University of Macau [SRG201800130-FHS]
- Science and Technology Development Fund, Macau SAR [0109/2018/A3, 0011/2019/AKP]
The study created a novel phenolic inducer through self-assembly, which enhances cell death triggered by doxorubicin and accelerates immunogenic cell death (ICD) induction, leading to increased infiltration of tumor-specific T cells and improved tumor response to PD-1 checkpoint blockade immunotherapy.
A critical challenge remains in PD-1 checkpoint blockade immunotherapy is few tumor specific T cells infiltration in hypoxic tumor microenvironment (TME). Improving immunogenic cell death (ICD) associated immunogenicity can make tumor sensitive to PD-1 checkpoint blockade immunotherapy. Herein, a phenolic ICD inducer was engineered by self-assembly of the superior ICD inducer (doxorubicin, DOX), phenolic manganese dioxide nanoreactor, ferric iron and PEG-polyphenols (MDP NPs) via metal phenolic coordination. These oxygen self-supporting MDP NPs strengthen DOX based ROS-dependent cell death and their metal mediated chemodynamic effect accelerate ICD induction. Together with concomitant ICD triggered by DOX, MDP NPs successively lead to tumor-associated antigen boosting, DCs maturation and ultimately enhance tumor-specific T cells infiltration. Furthermore, MDP NPs efficiently modulated hypoxic TME for effective macrophages recruitment. This promising ICD-augment strategy efficiently improve tumor response to PD-1 checkpoint blockade immunotherapy, resulting in a significant antitumor immune response in primary tumor and a strong abscopal effect to distant tumor. Our simple and versatile phenolic inducer expands the application of chemodrugs based ICD enhancing PD-1 checkpoint blockade immunotherapy.
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