Diselenide-Pemetrexed Assemblies for Combined Cancer Immuno-, Radio-, and Chemotherapies

Tianyu Li, Shuojiong Pan, Shiqian Gao, Wentian Xiang, Chenxing Sun, Wei Cao, Huaping Xu

Angew. Chem. Int. Ed., 2019, DOI: 10.1002/anie.201914453

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 nature killer (NK) cell-based cancer immunotherapy with radiotherapy and chemotherapy in a single system. The assemblies are prepared via co-assembly between pemetrexed and cytosine-containing diselenide through hydrogen bonds. Under γ-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, which reveals a new strategy for combination therapy in cancer treatment.

LiT Angew 2019