Targeted scavenging of extracellular ROS relieves suppressive immunogenic cell death

Hongzhang Deng, Weijing Yang, Zijian Zhou, Rui Tian, Lisen Lin, Ying Ma, Jibin Song () and Xiaoyuan Chen ()
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Hongzhang Deng: MOE key laboratory for analytical science of food safety and biology, College of Chemistry, Fuzhou University
Weijing Yang: Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)
Zijian Zhou: Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)
Rui Tian: Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)
Lisen Lin: MOE key laboratory for analytical science of food safety and biology, College of Chemistry, Fuzhou University
Ying Ma: Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)
Jibin Song: MOE key laboratory for analytical science of food safety and biology, College of Chemistry, Fuzhou University
Xiaoyuan Chen: Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-18745-6

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