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Peer-reviewedCC BY-NC 4.0Investigative and Clinical Urology

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

  • Sejung Maeng1
  • Mi Jeong Kim2
  • Mirinae Kim1
  • Jong Hyun Tae1
  • Se Young Choi1
  • Kyungchan Min1
  • In Ho Chang1
  • Hak Jong Lee2,3,4,5
  • Joongwon Choi6
  • Chung Un Lee6
  • Yong Seong Lee6
  • Jung Hoon Kim6
6 affiliations
  1. 1Department of Urology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea .
  2. 2Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea .
  3. 3Department of Medical Device Development, Seoul National University College of Medicine, Seoul, Korea .
  4. 4Department of Radiology, Seoul National University College of Medicine, Seoul, Korea .
  5. 5Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Korea .
  6. 6Department of Urology, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University College of Medicine, Gwangmyeong, Korea .
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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.

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Cite

BibTeXRIS
BibTeX
@article{maeng2026ultrasoundtriggered,
  title = {{Ultrasound-triggered release of gemcitabine-loaded liposomes enhances intravesical therapy for bladder cancer}},
  author = {Sejung Maeng and Mi Jeong Kim and Mirinae Kim and Jong Hyun Tae and Se Young Choi and Kyungchan Min and In Ho Chang and Hak Jong Lee and Joongwon Choi and Chung Un Lee and Yong Seong Lee and Jung Hoon Kim},
  journal = {Investigative and Clinical Urology},
  year = {2026},
  month = oct,
  doi = {10.4111/icu.20260076},
  url = {https://doi.org/10.4111/icu.20260076},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Ultrasound-triggered release of gemcitabine-loaded liposomes enhances intravesical therapy for bladder cancer
AU  - Sejung Maeng
AU  - Mi Jeong Kim
AU  - Mirinae Kim
AU  - Jong Hyun Tae
AU  - Se Young Choi
AU  - Kyungchan Min
AU  - In Ho Chang
AU  - Hak Jong Lee
AU  - Joongwon Choi
AU  - Chung Un Lee
AU  - Yong Seong Lee
AU  - Jung Hoon Kim
PY  - 2026
DA  - 2026/10/08
JO  - Investigative and Clinical Urology
DO  - 10.4111/icu.20260076
UR  - https://doi.org/10.4111/icu.20260076
AB  - 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.
SN  - 2466-0493
SN  - 2466-054X
ER  -