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

Despite 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. © 2023 Wiley-VCH GmbH.

Citation

Xiaofan Tang, Ye Yang, Mingbin Zheng, Ting Yin, Guojun Huang, Zhengyu Lai, Baozhen Zhang, Ze Chen, Tiantian Xu, Teng Ma, Hong Pan, Lintao Cai. Magnetic-Acoustic Sequentially Actuated CAR T Cell Microrobots for Precision Navigation and In Situ Antitumor Immunoactivation. Advanced materials (Deerfield Beach, Fla.). 2023 May;35(18):e2211509

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PMID: 36807373

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