Magnetic–Acoustic Sequentially Actuated CAR T Cell Microrobots for Precision Navigation and In Situ Antitumor Immunoactivation

Abstract

AbstractDespite its clinical success, chimeric antigen receptor T (CAR T)‐cell immunotherapy remains limited in solid tumors, owing to the harsh physical barriers and immunosuppressive microenvironment. Here a CAR‐T‐cell‐based live microrobot (M‐CAR T) is created by decorating CAR T with immunomagnetic beads using click conjugation. M‐CAR Ts are capable of magnetic–acoustic actuation for precision targeting and in situ activation of antitumor immune responses. Sequential actuation endows M‐CAR Ts with magnetically actuated anti‐flow and obstacle avoidance as well as tissue penetration driven by acoustic propulsion, enabling efficient migration and accumulation in artificial tumor models. In vivo, sequentially actuated M‐CAR Ts achieves long‐distance targeting and accumulate at the peritumoural area under programmable magnetic guidance, and subsequently acoustic tweezers actuate M‐CAR Ts to migrate into deep tumor tissues, resulting in a 6.6‐fold increase in accumulated exogenous CD8+ CAR T cells compared with that without actuation. Anti‐CD3/CD28 immunomagnetic beads stimulate infiltrated CAR T proliferation and activation in situ, significantly enhancing their antitumor efficacy. Thus, this sequential‐actuation‐guided cell microrobot combines the merits of autonomous targeting and penetration of intelligent robots with in situ T‐cell immunoactivation, and holds considerable promise for precision navigation and cancer immunotherapies.