Related Experiment Video
Updated: Jun 30, 2025
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
A Selective-Tumor-Penetrating Strategy via Unidirectional Direct Transfer for Intravesical Therapy of Bladder Cancer
Xiaowen Qin1, Heng Wang1, Wentao Xu2,3
1Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang 310000, China.
Abstract:
A selective tumor-penetrating strategy generally exploits tumor-targeted ligands to modify drugs so that the conjugate preferentially enters tumors and subsequently undergoes transcellular transport to penetrate tumors. However, this process shields ligands from their corresponding targets on the cell surface, possibly inducing an off-target effect during drug penetration at the tumor-normal interface. Herein, we first describe a selective tumor-penetrating drug (R11-phalloidin conjugates) for intravesical therapy of bladder cancer. The intravesical conjugates rapidly translocated across the mucus layer, specifically bound to tumors, and infiltrated throughout the tumor via direct intercellular transfer. Notably, direct transfer from normal cells to tumor cells was unidirectional because the pathways required for direct transfer, termed F-actin-rich tunneling nanotubes, were more unidirectionally extended from normal cells to tumor cells. Moreover, the intravesical conjugates displayed strong anticancer activity and well-tolerated biosafety in murine orthotopic bladder tumor models. Our study demonstrated the potential of a selective tumor-penetrating conjugate for effective intravesical anticancer therapy.
Insights
Researchers developed R11-phalloidin conjugates for bladder cancer, enabling selective tumor penetration and infiltration via intercellular transfer. This novel drug delivery system shows potent anticancer activity and good biosafety in preclinical models.
Area of Science:
- Oncology
- Drug Delivery
- Biotechnology
Background:
- Selective tumor penetration strategies often involve drug-ligand conjugates.
- Current methods may shield ligands, leading to off-target effects at tumor-normal interfaces.
- Intravesical therapy is a promising approach for bladder cancer treatment.
Purpose of the Study:
- To develop and evaluate a selective tumor-penetrating drug conjugate for intravesical bladder cancer therapy.
- To investigate the mechanism of tumor infiltration and intercellular transfer.
- To assess the anticancer efficacy and biosafety of the conjugate.
Main Methods:
- Synthesis of R11-phalloidin conjugates for intravesical administration.
- Evaluation of mucus layer translocation and tumor-specific binding.
- Analysis of intercellular transfer via F-actin-rich tunneling nanotubes.
- Assessment of anticancer activity and biosafety in murine orthotopic bladder tumor models.
Main Results:
- The intravesical conjugates demonstrated rapid mucus translocation and specific tumor binding.
- Efficient tumor infiltration was achieved through direct intercellular transfer.
- Unidirectional transfer from normal to tumor cells was observed via tunneling nanotubes.
- Strong anticancer activity and well-tolerated biosafety were confirmed in preclinical models.
Conclusions:
- R11-phalloidin conjugates represent a novel strategy for selective tumor penetration in bladder cancer.
- Direct intercellular transfer through tunneling nanotubes facilitates effective tumor infiltration.
- This approach holds potential for advanced intravesical anticancer therapy with favorable safety profiles.
