Targeted scavenging of extracellular ROS relieves suppressive immunogenic cell death

被引:197
作者
Deng, Hongzhang [1 ,2 ]
Yang, Weijing [2 ]
Zhou, Zijian [2 ]
Tian, Rui [2 ]
Lin, Lisen [1 ]
Ma, Ying [2 ]
Song, Jibin [1 ]
Chen, Xiaoyuan [2 ]
机构
[1] Fuzhou Univ, Coll Chem, MOE Key Lab Analyt Sci food Safety & Biol, Fuzhou 350108, Peoples R China
[2] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA
基金
美国国家卫生研究院; 中国国家自然科学基金;
关键词
ISOTHERMAL TITRATION CALORIMETRY; CANCER; ROLES;
D O I
10.1038/s41467-020-18745-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Immunogenic cell death (ICD) and tumour-infiltrating T lymphocytes are severely weakened by elevated reactive oxygen species (ROS) in the tumour microenvironment. It is therefore of critical importance to modulate the level of extracellular ROS for the reversal of immunosuppressive environment. Here, we present a tumour extracellular matrix (ECM) targeting ROS nanoscavenger masked by pH sensitive covalently crosslinked polyethylene glycol. The nanoscavenger anchors on the ECM to sweep away the ROS from tumour microenvironment to relieve the immunosuppressive ICD elicited by specific chemotherapy and prolong the survival of T cells for personalized cancer immunotherapy. In a breast cancer model, elimination of the ROS in tumour microenvironment elicited antitumour immunity and increased infiltration of T lymphocytes, resulting in highly potent antitumour effect. The study highlights a strategy to enhance the efficacy of cancer immunotherapy by scavenging extracellular ROS using advanced nanomaterials. Reactive oxygen species in the tumour microenvironment can have an immunosuppressive effect. Here, the authors devise a nanoparticle that anchors to the extracellular matrix within tumours and scavenges reactive oxygen species, resulting in an enhanced immune response within the tumour.
引用
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页数:12
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