Anti-biopassivated Reticular Micromotors for Bladder Cancer Therapy

The limited lifespan of enzyme-powered micro/nanomotors (MNMs) hinders their biomedical applications due to the easy deactivation in tumor microenvironments. In this study, by taking advantage of hydrogen bond-rich metal-organic frameworks (MOFs), we design anti-biopassivated urease-powered MOF motors (Ur-MOFtors) with sustained motility for bladder cancer therapy. Such reticular Ur-MOFtors exhibited an exceptionally long locomotion lifespan exceeding 90 min in highly concentrated urea, which was an 18-fold enhancement compared with urease-adsorbed MOFs, resulting in excellent anti-biopassivation of MOFtors. The underlying molecular mechanism of persistent motion involves hydrogen bonding interaction between the MOF skeleton and the catalytic product, as identified by <i>in situ</i> infrared spectroscopy and density functional theory. Based on the preserved enzymatic activity comparable to native urease, the self-propulsion pathway of Ur-MOFtors is driven by ionic self-diffusiophoresis with the positive chemotactic motion toward urea. Benefiting from the persistent motion of Ur-MOFtors in physiological urea, a rapid bladder cancer therapy was achieved with few instillation sessions and short treatment cycles during intravesical administration. This hydrogen bond-rich framework presents a promising anti-biopassivated approach to overcoming the short lifespan and easy deactivation of enzymatic motors for advanced therapeutic robotics.