Work

Ultrasound-triggered release of gemcitabine-loaded liposomes enhances intravesical therapy for bladder cancer

Year: 2026

Type: article

Abstract: PURPOSE: Intravesical chemotherapy for bladder cancer is limited by insufficient urothelial drug penetration and rapid drug washout. We developed an ultrasound-responsive liposomal formulation that encapsulates gemcitabine to enable controlled intravesical drug release using a clinically available ultrasound system. MATERIALS AND METHODS: Gemcitabine-loaded liposomes (GEM-Lipo) were manufactured and characterized for their physicochemical properties and ultrasound-responsive drug release. Human bladder cancer cell lines (T24, 253J, and 5637) were evaluated in two-dimensional (2D) monolayer and three-dimensional (3D) spheroid cultures to assess cytotoxicity and intracellular drug uptake following ultrasound exposure (1.0-1.5 MHz). Therapeutic efficacy and safety were further investigated in an orthotopic MBT2-luciferase bladder cancer mouse model using intravesical GEM-Lipo combined with ultrasound treatment and longitudinal bioluminescence imaging. RESULTS: Ultrasound exposure (1.5 MHz, 1 minute) significantly enhanced gemcitabine release from the liposomal carriers (p<0.01), resulting in increased intracellular drug accumulation and reduced cancer cell viability in both 2D and 3D cultures. Ultrasound-assisted delivery further augmented the cytotoxic effects of GEM-Lipo in spheroid cultures compared with liposomal treatment alone (p<0.01). The combination of GEM-Lipo and ultrasound produced the most pronounced suppression of orthotopic bladder tumor growth, as evidenced by the decreased bioluminescence signal (p<0.01), without detectable systemic toxicity. CONCLUSIONS: Clinically available ultrasound can activate GEM-Lipo, enhancing intravesical drug delivery and antitumor efficacy while maintaining safety. This platform offers a practical and translatable strategy for bladder-preserving therapy in non-muscle invasive bladder cancer.

Source: Korean journal of urology

DOI: 10.4111/icu.20260076