pH-Sensitive Magnetic Nanoparticle-Mediated Natural-Killer-Cell-Based Microrobots for Dual-Targeted Delivery and Induction of Pro-Inflammatory Macrophage Polarization

Adoptive cell therapy using natural killer (NK) cells emerges as the next-generation cancer immunotherapy. Based on the intrinsic capability of direct cancer cell necrosis without prior education, a chemotherapeutic, free-drug delivery, NK-cell-based platform can be developed. However, weak targeting of NK cells to solid tumors is observed. In addition, to boost the tumor-killing efficiency, another immune-regulating function should be added to the cells. Herein, a NK-cell-based hybrid system (NK-Robot) conjugated with magnetic nanoparticles (MNPs) that provides 1) efficient guidance of NK cells and 2) targeted delivery of MNPs in situ is demonstrated, taking advantage of a newly designed, stimuli-responsive polymeric linker. Thus, NK cells are allowed to target tumors under magnetic control conditions, and the liberated MNPs effectively reeducate the tumor-associated macrophages (M2) to antitumor macrophages (M1), beneficial for the immunotherapy of tumors. In vivo experiments on BALB/c nude mice further support the finding that NK-Robots effectively inhibit tumor growth.