Biomimetic Self-Guiding Nanomotors Boost Active Immunotherapy

Efficient and precise delivery of chemotherapeutic drugs with deep tumor penetration is critically significant for tumor therapy. Unfortunately, the therapeutic efficacy of traditional passive nanomedicines is still limited by insufficient biological barrier penetration and inadequate release of damage-associated molecular patterns (DAMPs). Herein, a biomimetic Janus HZ-AD nanomotor system with biosignal sensing and energy conversion capabilities is first demonstrated. l-Arginine is incorporated into the hollow and urchin-like Au nanoparticles, while ZIF8 is asymmetrically decorated on one side, incorporating DOX loading. The developed nanomotors are capable of self-navigating to the tumor site, leveraging the chemotactic behavior of arginine to autonomously steer to higher concentrations of hydrogen peroxide, thereby enhancing the deep tumor penetration based on active motion actuated by NIR irradiation. Meanwhile, the active nanomotors also facilitate cellular uptake with the subsequent release of DOX and a considerable amount of Zn²⁺, further inducing pyroptosis and increasing the immunogenicity of tumor cells, thereby activating the immune response and inhibiting the tumor growth, recurrence, and metastasis. By adopting a spatially and temporally regulated trimodality therapy strategy of chemotactic targeting, motion-induced deep penetration, and photochemoimmunotherapy, the developed nanomotors address the existing challenges in tumor therapy and allow for possible therapeutic advancements.