Journal
NANO LETTERS
Volume 19, Issue 8, Pages 4879-4889Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.9b00584
Keywords
Drug delivery; immunotherapy; immune checkpoint blockade; bioresponsive; nanomedicine
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Funding
- Jonsson Comprehensive Cancer Center at UCLA
- Alfred P. Sloan Foundation (Sloan Research Fellowship)
- Collaborative Innovation Center of Suzhou Nano Science Technology
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- 111 Project
- Joint International Research Laboratory of Carbon-Based Functional Materials and Devices
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Despite the promising efficacy of immune checkpoint blockade (ICB) in treating many types of cancers, the clinical benefits have often been restricted by the low objective response rates and systemic immune-related adverse events. Here, a bioresponsive ICB treatment is developed based on the reactive oxygen species (ROS)-sensitive protein complex for controlled sequential release of anti- don't eat me signal antibody (aCD47) and antiprogrammed cell death protein 1 (aPD1), by leveraging the abundant ROS in the tumor microenvironment (TME). These protein complexes can also act as scavengers of ROS in the TME to reverse the immunosuppressive responses, thereby enhancing antitumor efficacy in vivo. In a melanoma cancer model, the synergistic antitumor efficacy was achieved, which was accompanied by enhanced T cell immune responses together with reduced immunosuppressive responses.
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