Multifunctional Nanomotors with Aggregation-Induced NIR-II Emission and Photothermal Propulsion for Deep Tumor Penetration and Precise Phototheranostics.

The advent of photothermal-driven nanomotors presents exciting opportunities for tumor therapy. However, significant potential remains for improving the permeability of these nanomotors to tumors due to the barrier posed by the tumor stromal microenvironment (TSM). Additionally, advancing their functional integration in photothermal production and second near-infrared (NIR-II) imaging could enable deep-tissue phototheranostics. Herein, we develop multifunctional nanomotors by coating the exquisitely designed aggregation-induced emission (AIE) luminogen onto one hemisphere of the Janus dual-mesoporous silica using a pore-size-selective assembly strategy. Upon laser irradiation, these nanomotors not only emit strong NIR-II fluorescence for tumor diagnosis but also generate effective photothermal heat to induce thermophoresis. Meanwhile, the heat can disrupt tumor stromal structure, thereby reducing the resistance of TSM and facilitating effective propulsion, which improve cellular uptake, transvascular extravasation, and intratumoral penetration. This integrated nanoplatform significantly enhances the efficacy of synergistic active-motion photothermal therapy and chemotherapy, offering a promising strategy for deep tumor penetration and precise phototheranostics.