Labeling IL-18 with alkaloids: toward the use of cytokines as carrier molecules in chemotherapy

Abstract

Recent in vivo models demonstrated that immune checkpoint cancer therapy can be improved by injecting interleukine (IL)-18, a proinflammatory cytokine of the IL-1 family. Aiming to increase the beneficial action of cytokines in cancer treatments, we used docking, non-covalent interaction analysis and molecular dynamics simulations to determine their ability for embedding alkaloid-based drugs. Our calculations suggest that three alkaloids with anticancer activity, e.g., paclitaxel, vincristine and vinorelbine, can be used to efficiently stabilize the crystal-tetrameric form of IL-18 while being retained in their core region. The reported results pave a new synthetic route for designing bifunctional host–guest systems with an enhanced biological activity.