Enhanced urease-driven nanobots for radionuclide-based bladder cancer therapy

Bladder cancer treatment with intravenous medication delivery has reasonable survival rates but modest therapeutic efficacy. Taking advantage of their superior diffusion and mixing capacities in urine compared to traditional pharmaceuticals or passive nanoparticles, self-propelled nanoparticles, also known as nanobots, have been proposed as a solution to the latter issue. Nonetheless, nothing is known about how well nanobots can translate into bladder cancer treatments. Here, urease-powered, radiolabelled mesoporous silica-based nanobots were evaluated in an orthotopic animal model of bladder cancer. Both in vivo and ex vivo findings showed increased accumulation of nanobots at the tumor location; positron emission tomography in vivo showed an eight-fold increase. The ex vivo tumor penetration by nanobots was validated by label-free optical contrast based on polarization-dependent scattered light-sheet microscopy of cleared bladders. Intravesically treatment was given to tumor-bearing mice. About 90% less tumor size was observed when radio-iodinated nanobots were used for radionuclide therapy, establishing nanobots as effective delivery nanosystems for bladder cancer treatment.