Nanomotor-Assisted Intravesical Chemotherapy for Bladder Tumor Reduction and Suppression of Early Tumor Regrowth.

Abstract

Nanoparticles are widely used in nanomedicine for controlled drug delivery and improved bioavailability. However, their effectiveness is often limited by passive diffusion, especially in confined, fluid-filled environments like the bladder, where rapid drug clearance and uneven distribution reduce therapeutic impact. These challenges contribute to high recurrence in bladder cancer despite intravesical chemotherapy. To address this limitation, we present urease-powered nanomotors (NM) based on mesoporous silica nanoparticles loaded with Mitomycin C (MMC), the standard chemotherapeutic for nonmuscleinvasive bladder cancer. These NM useurea present in urine to induce motion and drug dispersion. <i>In vitro</i>, NM showed 2.3-fold higher uptake in mouse bladder cancer cells than passive nanoparticles and achieved the efficacy of free MMC (577.5 μg/mL) at a 20-fold lower dose (30 μg/mL). <i>In vivo</i>, a single intravesical dose reduced tumor volumes by 83% and prevented early tumor regrowth, demonstrating the potential of NM-based delivery for bladder cancer therapy.