Abstract
Background: Conventional intravesical chemotherapy for bladder cancer has shown limited clinical efficacy. To overcome this challenge, self-propelled nanomotors, including urease-modified nanomotors, have been developed. These nanomotors enhance drug diffusion in urine, offering advantages over traditional drugs and passive nanoparticles. However, a key issue remains: the inability to maintain long-term urease activity. Methods: Nanozymes, glucose oxidase, and urease are synthesized into a three-enzyme nanomotors via biomineralization, serving as a power source. Cell membrane nanoparticles loaded with gemcitabine were combined with three-enzyme nanomotors to form dual-spherical nanomotors. TEM, DLS, and analyses of urease/glucose oxidase activity and nanomotor trajectories confirmed successful nanomotor fabrication. These nanomotors can regulate tumor cell glucose metabolism and release gemcitabine upon cellular entry, achieving a dual anticancer effect. Results: Nanomotors synthesized through biomineralization methods exhibit the ability to retain long-term activity. After intravesical instillation, urease-containing nanomotors decomposed urea to produce carbon dioxide and ammonia, propelling rapid nanoparticle movement for deep bladder wall penetration. The homing ability of the tumor membrane-coated nanoparticles enhanced nanomotor accumulation in tumor cells. Subsequently, the nanomotors release Gox and gemcitabine, which significantly inhibit tumor progression. Conclusion: This innovative strategy utilizes gemcitabine - loaded nanomotors to penetrate the mucus layer and target tumors, inducing cell death for the treatment of bladder cancer.