Nanomaterials for Natural Killer Cell-Based Immunoimaging and Immunotherapies in Cancer

Natural killer (NK) cells are an important component of the tumor immunosurveillance; activated NK cells can recognize and directly lyse tumor cells eliciting a potent antitumor immune response. Due to their intrinsic ability to unleash cytotoxicity against tumor cells, NK cell-based adoptive cell therapies have gained rapid clinical significance, and many clinical trials are ongoing. However, priming and activating NK cells, infiltration of activated NK cells in the immunosuppressive tumor microenvironment, and tracking the infiltrated NK cells in the tumors remain a critical challenge. To address these challenges, NK cells have been successfully interfaced with nanomaterials where the morphology, composition, and surface characteristics of nanoparticles (NPs) were leveraged to enable longitudinal tracking of NK cells in tumors or deliver therapeutics to prime NK cells. Distinct from other published reviews, in this tutorial review, we summarize the recent findings in the past decade where NPs were used to label NK cells for immunoimaging or deliver treatment to activate NK cells and induce long-term immunity against tumors. We discuss the NP properties that are key to surmounting the current challenges in NK cells and the different strategies employed to advance NK cells-based diagnostics and therapeutics. We conclude the review with an outlook on future directions in NP-NK cell hybrid interfaces, and overall clinical impact and patient response to such interfaces that need to be addressed to enable their clinical translation.