Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 59, Issue 7, Pages 2700-2704Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201914453
Keywords
cancer immunotherapy; gamma radiation; pemetrexed; selenium; self-assembly
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Funding
- National Basic Research Program of China [2018YFA0208900]
- China National Funds for Distinguished Young Scientists [21425416]
- National Natural Science Foundation of China [21734006]
- Funds for Creative Research Groups of China of the National Natural Science Foundation of China [21821001]
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Immunotherapy has emerged as a promising new approach for cancer treatment. However, clinically available drugs have been limited until recently, and the antitumor efficacy of most cancer immunotherapies still needs to be improved. Herein, we develop diselenide-pemetrexed assemblies that combine natural killer (NK) cell-based cancer immunotherapy with radiotherapy and chemotherapy in a single system. The assemblies are prepared by co-assembly between pemetrexed and cytosine-containing diselenide through hydrogen bonds. Under gamma-radiation, the hydrogen bonds are cleaved, resulting in the release of pemetrexed. At the same time, diselenide can be oxidized to seleninic acid, which suppresses the expression of human leukocyte antigen E (HLA-E) in cancer cells, thus activating the immune response of NK cells. In this way, cancer immunotherapy is combined with radiotherapy and chemotherapy, providing a new strategy for cancer treatment.
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