MoN/Au/cTAT Boosted Sonochemotherapy Post-Intravesical Instillation in Bladder Cancer

Intravesical chemotherapy is effective for non-muscle-invasive bladder cancer (NMIBC) but limited in muscle-invasive bladder cancer (MIBC) due to poor tissue penetration, underscoring the need for alternative dynamic treatment strategies. Sonochemotherapy (SCT), which combines ultrasound-triggered reactive oxygen species (ROS) generation with controlled drug release, presents a promising approach. Given the superficial anatomical location of the bladder, SCT's deep tissue penetration and favorable safety profile make it particularly suitable for bladder cancer treatment. However, SCT efficacy is frequently constrained by insufficient ROS production and sonosensitizer instability. To overcome these challenges, a MoN/Au/cTAT nanocomposite was developed by conjugating cisplatin and human immunodeficiency virus-1 transcription activator (cTAT) onto MoN/Au nanosheets to enhance the stability and the effect of SCT. As a result, MoN/Au/cTAT demonstrates potent cytotoxicity against bladder cancer cells under ultrasound irradiation. In vivo, it effectively suppresses muscle-invasive orthotopic bladder tumors while maintaining a high safety margin. In summary, the nanosonosensitizer-chemodrug platform combines cTAT for improved transmucosal delivery and tumor penetration with MoN/Au to efficiently generate ROS under ultrasound irradiation, offering a transformative strategy for muscle-invasive bladder cancer therapy.