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Updated: Jun 12, 2025
A Murine Orthotopic Bladder Tumor Model and Tumor Detection System
Published on: January 12, 2017
Intravesical Tumor-Selective Mucoadhesive Hydrogel for Effective Chemotherapy In Murine Model
Bin Zheng1,2, Zheng Chen1, Luping Sun1
1Department of Urology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, People's Republic of China.
Introduction:
The therapeutic efficacy of intravesical agents for bladder cancer (BCa) is frequently constrained by their clearance via urine flushing and periodic bladder emptying, as well as the absence of tumor-targeting capabilities. Consequently, an effective drug delivery system must possess both tumor-targeting and adhesion properties to overcome these limitations.
Methods:
In this study, we investigated a tumor-selective hydrogel as a potential vehicle for BCa treatment. For the first time in the field of intravesical therapy, we introduced the concept of pre-targeting, sequentially instilling modified polyarginine and membrane nanoparticles into the bladder to achieve selective gelation on the tumor surface. We comprehensively evaluated tumor selectivity, endocytosis pathways, organelle localization, and osmotic capacity, and demonstrated in vivo and in vitro degradation following drug delivery.
Results:
The pre-targeted hydrogel exhibited superior tumor selectivity. The drug-loaded membrane nanoparticles released during hydrogel degradation were internalized by tumor cells at levels exceeding those in normal cells by more than eightfold. Our findings indicated that this internalization process was energy-dependent and mediated by caveolin. Post-internalization, the drug-loaded membrane nanoparticles localized to the endoplasmic reticulum and Golgi apparatus, with minimal colocalization with lysosomes. Moreover, the hydrogel demonstrated profound penetration into tumor tissue. In terms of antitumor efficacy, the hydrogel loaded with gemcitabine exhibited significantly enhanced therapeutic effects compared to free gemcitabine.
Conclusion:
Our dual-functional hydrogel system exhibits robust anti-tumor activity against BCa, presenting a promising alternative for intravesical therapy. This innovative approach addresses key limitations of current treatments by combining tumor targeting with sustained drug adhesion, offering a novel strategy for the management of BCa.
Insights
A novel dual-functional hydrogel system enhances bladder cancer (BCa) treatment by targeting tumors and improving drug adhesion. This pre-targeted hydrogel shows significant anti-tumor activity, offering a promising alternative for intravesical therapy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Intravesical agents for bladder cancer (BCa) face limitations due to rapid clearance and lack of tumor targeting.
- Effective drug delivery requires tumor-specific adhesion and retention properties.
Purpose of the Study:
- To investigate a tumor-selective hydrogel as a novel intravesical drug delivery vehicle for BCa treatment.
- To introduce and evaluate a pre-targeting strategy for enhanced BCa therapy.
Main Methods:
- Developed a dual-functional hydrogel system using sequential instillation of modified polyarginine and membrane nanoparticles.
- Assessed tumor selectivity, nanoparticle uptake pathways, organelle localization, and degradation.
- Evaluated in vitro and in vivo antitumor efficacy of gemcitabine-loaded hydrogel.
Main Results:
- The pre-targeted hydrogel demonstrated superior tumor selectivity and profound tumor tissue penetration.
- Drug-loaded nanoparticles showed over eightfold higher internalization by tumor cells versus normal cells, mediated by caveolin.
- Gemcitabine-loaded hydrogel exhibited significantly enhanced therapeutic effects compared to free gemcitabine.
Conclusions:
- The dual-functional hydrogel system exhibits robust anti-tumor activity against BCa.
- This innovative approach addresses limitations of current intravesical therapies by combining tumor targeting and sustained drug adhesion.
- Presents a promising novel strategy for BCa management.
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