Urease-Powered Nanobots for Enhanced Radionuclide Therapy in Bladder Cancer

This year, we published a study in Nature Nanotechnology exploring the potential of enzyme-powered nanobots as an innovative approach for radionuclide therapy in bladder cancer. Current intravesical treatments for non-muscle-invasive bladder cancer (NMIBC), such as Bacillus Calmette–Guérin (BCG) immunotherapy and chemotherapy, have shown limited efficacy due to poor drug retention and distribution. To address these limitations, we designed and tested urease-powered nanobots composed of mesoporous silica nanoparticles (MSNPs) radiolabeled with iodine-131 (¹³¹I). These nanobots exhibit active self-propulsion in the bladder environment, significantly enhancing their accumulation at tumor sites. Using in vivo and ex vivo imaging techniques, including positron emission tomography (PET) and scattered light-sheet microscopy, we demonstrated an eightfold increase in tumor retention compared to passive nanoparticles. The nanobot-based therapy led to a remarkable 90% tumor size reduction in an orthotopic murine model, outperforming traditional treatments.Our findings highlight the advantages of enzyme-powered nanobots in overcoming key barriers in bladder cancer therapy, such as drug sedimentation and low tissue penetration. By harnessing endogenous urea as fuel, these nanobots navigate through complex biological fluids and accumulate efficiently at tumor sites, ensuring effective delivery of radionuclide therapy. The study paves the way for the clinical translation of nanobot-based therapeutics, offering a promising alternative to conventional NMIBC treatments with reduced systemic side effects. Future research will focus on optimizing this approach for human applications and exploring its potential for other localized cancers.The work has massively attracted the attention from the media with a top record of 567 online apperances (Number 1 media coverage for the journal Nature Nanotech.).