NIR-II Light-Actuated Nanomotors for Enhanced Photoimmunotherapy Toward Hepatocellular Carcinoma

Light-propelled nanomotors, which can convert external light into mechanical motion, have shown considerable potential in the construction of a new generation of drug delivery systems. However, the therapeutic efficacy of light-driven nanomotors is always unsatisfactory due to the limited penetration depth of near-infrared-I (NIR-I) light and the inherent biocompatibility of the motor itself. Herein, an asymmetric nanomotor (Pd@ZIF-8/R848@M JNMs) with efficient motion capability is successfully constructed for enhanced photoimmunotherapy toward hepatocellular carcinoma. Under near-infrared-II (NIR-II) irradiation, Pd@ZIF-8/R848@M JNMs convert light energy into heat energy, exhibiting self-thermophoretic locomotion to penetrate deeper into tumor tissues to achieve photothermal therapy. At the same time, functionalized with an immune-activated agent Resiquimod (R848), our nanomotors could convert a “cold tumor” into a “hot tumor”, transforming the immunosuppressive microenvironment into an immune-activated state, thus achieving immunotherapy. Dual photoimmunotherapy of the as-developed NIR-II light-driven Pd@ZIF-8/R848@M JNMs demonstrates considerable tumor inhibition effects, offering a promising therapeutic approach in the field of anticancer therapy.