Selenopeptide Nanomedicine Activates Natural Killer Cells for Enhanced Tumor Chemoimmunotherapy

Chemoimmunotherapy using nanotechnology has shown great potential for cancer therapy in the clinic. However, uncontrolled transportation and synergistic responses remain challenges. Here, a self‐assembled selenopeptide nanoparticle that strengthens tumor chemoimmunotherapy through the activation of natural killer (NK) cells by the oxidative metabolite of the selenopeptide is developed. With the advantages of the enzyme‐induced size‐reduction and the reactive‐oxygen‐species‐driven deselenization, this selenopeptide is able to deliver therapeutics, e.g., doxorubicin (DOX), to solid tumors and further activate the NK cells in a programmed manner. Importantly, in vitro and in vivo results prove the mutual promotion between the DOX‐induced chemotherapy and the selenopeptide‐induced immunotherapy, which synergistically contribute to the improved antitumor efficacy. It is anticipated that the selenopeptide may provide a type of promising stimuli‐responsive immune modulator for versatile biomedical applications. A self‐assembled selenopeptide nanomedicine is developed to strengthen chemoimmunotherapy through combing the programmable delivery of doxorubicin and the synergistic NK cell immunotherapy activated by oxidative seleno‐metabolites. The xperimental results demonstrate the mutual promotion between the doxorubicin‐induced chemotherapy and the selenopeptide‐induced immunotherapy, which synergistically contribute to improved antitumor efficacy.