Intravesical Tumor-Selective Mucoadhesive Hydrogel for Effective Chemotherapy In Murine Model

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.