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.