Magnetic-Acoustic Sequentially Actuated CAR T Cell Microrobots for Precision Navigation and In Situ Antitumor Immunoactivation.
Adv Mater
; 35(18): e2211509, 2023 May.
Article
en En
| MEDLINE
| ID: mdl-36807373
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores Quiméricos de Antígenos
/
Neoplasias
Tipo de estudio:
Guideline
Límite:
Humans
Idioma:
En
Revista:
Adv Mater
Asunto de la revista:
BIOFISICA
/
QUIMICA
Año:
2023
Tipo del documento:
Article
Pais de publicación:
Alemania