Radionuclide therapy based on accumulated urease-powered nanobots in the bladder tumor of an orthotopic murine model

Abstract Bladder cancer (BC) is among the most common cancers worldwide. Current treatment methods involving intravesical drug administration present good survival rates but low therapeutic efficacy. Self-propelled nanoparticles (nanobots) could overcome these limitations through their enhanced diffusion and mixing capabilities in urine compared to conventional drugs or passive nanoparticles. Here, we radiolabeled mesoporous silica-based urease-powered nanobots for imaging purposes and tested them in an orthotopic murine model of BC. In vivo and ex vivo results demonstrate enhanced accumulation of nanobots at the tumor site. Positron emission tomography revealed an 8-fold increase in accumulation in vivo. Inductively coupled plasma mass spectrometry confirmed these results. A custom label free optical contrast based on polarization-dependent scattered lightsheet microscopy was applied to cleared bladders to confirm tumor penetration by nanobots. Treating tumor-bearing mice with intravesically administered radio-iodinated nanobots for radionuclide therapy resulted in tumor size reductions of about 90% compared with non-treated mice, positioning nanobots as efficient delivery nanosystems for BC therapy.