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.

Automated summary

Nanotechnology-based chemoimmunotherapy has shown great potential for cancer treatment, but uncontrolled transportation and synergistic responses remain challenges. In this study, a self-assembled selenopeptide nanoparticle is developed to enhance tumor chemoimmunotherapy by activating natural killer (NK) cells through the oxidative metabolite of the selenopeptide. By leveraging the advantages of size reduction and deselenization driven by reactive oxygen species, this selenopeptide can deliver therapeutics, such as doxorubicin (DOX), to solid tumors and programmatically activate NK cells. In vitro and in vivo results demonstrate the synergistic effect between DOX-induced chemotherapy and selenopeptide-induced immunotherapy, leading to improved antitumor efficacy. The selenopeptide holds promise as a stimuli-responsive immune modulator for versatile biomedical applications.