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 in situ 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.