(UroToday.com) The American Urological Association's 2026 Annual Meeting, in Washington D.C., was host to the Interactive Poster (IP20): Bladder Cancer: Non-invasive II session. Dr. Shi Fu presented interactive poster 20-08 Thermo-sensitive Hydrogel System Enables Sustained Intravesical Delivery of Antibody–Drug Conjugates for Effective Treatment of Non–Muscle-Invasive Bladder Cancer.
Dr. Fu highlighted that antibody–drug conjugates (ADCs) have demonstrated significant clinical activity in bladder cancer, particularly in advanced disease. However, translating this success to the non–muscle-invasive setting has been challenging. Intravesical delivery of ADCs remains limited by several practical barriers, including drug instability within the bladder environment, short residence time requiring frequent instillations, and the associated high treatment costs.
Dr. Fu and colleagues developed a novel intravesical ADC delivery platform using a thermo-sensitive ALG-NIPAM hydrogel. This system is administered as a liquid at 25 °C and rapidly transitions into a gel at body temperature, allowing for prolonged intravesical residence and sustained drug release.
To model this process, a Transwell co-culture system was used to simulate controlled drug exposure. The structural integrity of the encapsulated monoclonal antibody was rigorously evaluated using multiple analytical techniques, including UV spectroscopy, SDS-PAGE, SEC-HPLC, and dynamic light scattering. Drug–antibody ratio stability was assessed with HIC-HPLC, while LC-MS/MS was used to evaluate payload deconjugation. Antitumor activity of disitamab vedotin encapsulated within the hydrogel was subsequently evaluated in both in vitro and in vivo models.
The figure below illustrates the physicochemical properties and functional performance of the ALG-NIPAM hydrogel delivery system. The platform demonstrates a reversible sol–gel transition, remaining in liquid form at 25 °C and rapidly forming a gel at 37 °C, supporting its intravesical applicability. Structural characterization by SEM confirms a porous network, while FTIR analyses validate successful incorporation of the ADC into the hydrogel matrix. UV-Vis studies show stable release profiles across different media, including urine and varying pH conditions, with sustained drug release over time. Quantitative release assays further confirm gradual and prolonged release kinetics. Fluorescence imaging demonstrates effective cellular uptake of DV at ALG-NIPAM in bladder cancer cells, comparable to the free drug, supporting preserved biological activity with this delivery approach.
Moreover, Dr Fu Highlighted that the hydrogel-based delivery system demonstrated preservation of antibody stability and functional integrity across multiple conditions. Importantly, the encapsulated ADC maintained its structural stability without evidence of aggregation, conformational changes, or payload deconjugation in different pH environments and in urine. Sustained drug release was observed, with peak release occurring at approximately 96 hours. Fluorescence-based uptake assays showed that Disitimab vedotin (DV) at ALG-NIPAM achieved comparable internalization to free disitamab vedotin in HER2-positive cells, with uptake increasing over time, supporting effective cellular delivery despite encapsulation.
From a functional standpoint, DV at ALG-NIPAM exhibited antitumor activity equivalent to free DV in HER2-positive models, but with a more sustained effect over time. Notably, the hydrogel formulation induced more robust and durable immunogenic cell death compared to free drug, suggesting potential added immunologic benefit beyond cytotoxicity. These findings support that controlled release does not compromise efficacy and may enhance biological activity.
In vivo, intravesical administration of DV at ALG-NIPAM in the BBN-induced bladder cancer model (as shown below) resulted in a significant reduction in tumor burden compared to free DV. Drug retention was markedly prolonged, with tumor-associated fluorescence persisting up to 168 hours in the hydrogel group versus only 8 hours with free drug. Pathologic evaluation confirmed smaller tumors in the hydrogel-treated group, without differences in body weight or evidence of increased systemic toxicity, supporting both efficacy and tolerability of this approach.
Dr. Fu concluded with the following key points:
- A novel thermo-sensitive hydrogel platform enables sustained and stable intravesical delivery of ADCs
- This approach enhances antitumor efficacy compared with conventional delivery strategies
- The system may promote synergistic activity when combined with immune checkpoint blockade
- Prolonged drug release could reduce the need for frequent instillations and improve treatment practicality
- This platform represents a promising strategy to optimize intravesical ADC therapy in bladder cancer while potentially reducing overall treatment costs
Presented by: Shi Fu, Professor Department of Urology at The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China.
Written by: Julian Chavarriaga, MD, Clinical Assistant Professor, Urologic Oncologist, Department of Urology at Penn State Health @chavarriagaj on Twitter during the American Urological Association (AUA) 2026 Annual Meeting, Washington, DC, Fri, May 15 – Mon, May 18, 2026.