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

作者：Bin Zheng, Zheng Chen, Luping Sun, Jing Quan, Jianwen Wei, Bao-Yuan Huang, Dahong Zhang, Pu Zhang, Yumin Zhuo · 发表于：International Journal of Nanomedicine · 年份：2025 · DOI：10.2147/ijn.s522421 · 被引用次数：5 · 研究领域：Bladder and Urothelial Cancer Treatments、Tissue Engineering and Regenerative Medicine、Urinary Bladder and Prostate Research

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 tum...