Urease-Powered Nanomotors for Enhanced Mucosal and Tumor Penetration To Augment Sonodynamic Therapy in Bladder Cancer

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Bladder cancer treatment is challenged by mucosal barriers and bladder voiding.
• Sonodynamic therapy (SDT) shows promise but requires improved drug delivery and retention.
• Existing intravesical therapies face limitations due to the bladder's physiological environment.

Purpose of the Study:

• To engineer self-propelled nanomotors for enhanced intravesical sonodynamic therapy (SDT) in bladder cancer.
• To overcome the glycosaminoglycan mucosal barrier and reduce washout during micturition.
• To improve drug accumulation and therapeutic efficacy at the tumor site.

Main Methods:

• Urine-derived exosomes (EXO) were engineered into nanovesicles (NVs) coencapsulating urease and a sonosensitizer (tetrakis (4-carboxyphenyl) porphyrin).
• Nanovesicles (NVs) were propelled by urease-catalyzed urea decomposition, generating CO2 and ammonia.
• In vivo studies involved intravesical administration of NVs in mice with bladder cancer, followed by ultrasound irradiation.

Main Results:

• Self-propelled NVs demonstrated significantly enhanced infiltration into bladder mucosal tissues compared to static controls.
• Improved drug accumulation and retention within the tumor site were observed with propelled NVs.
• Ultrasound-activated SDT using propelled NVs resulted in superior tumor growth suppression and extended animal survival.

Conclusions:

• Self-propelled nanovesicles effectively overcome bladder mucosal barriers and physiological washout.
• This nanomotor-based platform potentiates sonodynamic therapy for enhanced bladder cancer treatment.
• The engineered nanovesicles offer a promising strategy for minimally invasive and effective bladder cancer therapy.