A gel system for single instillation of non-muscle-invasive bladder Cancer: A “divide-and-rule” strategy

• DOI: 10.1016/j.jconrel.2018.06.036
• Publication Date: 2018-07-02T17:54:53Z
• Authors: Pengyu Guo; Wenting Shang; Li Peng; Lu Wang; Hongzhi Wang; Ziyu Han; Hongmei Jiang; Jie Tian; Kun Wang; Wanhai Xu
• Keywords: Dendrimers; Mice, Inbred BALB C; Mice, Nude; Antineoplastic Agents; Dextrans; Deoxycytidine; Gemcitabine; Polyethylene Glycols; 3. Good health; Mice; 03 medical and health sciences; Administration, Intravesical; Drug Delivery Systems; 0302 clinical medicine; Urinary Bladder Neoplasms; Doxorubicin; Animals; Female; Gels

Single instillation (SI) reduces recurrence of non-muscle-invasive bladder cancer by chemoresecting floating tumor cells and residual tumor lesions (RTLs) after transurethral resection of the bladder, but with limited efficacy. Current studies improved this by prolonging retention time and increasing penetration to bladder wall, ignoring that the two separate factors should be treated in different ways. Here, we introduced a smart gel system-based SI to prevent re-implantation of tumor cells (RTCs) and ablate RTLs in a "divide-and-rule" approach. The gel system was synthesized by PEG-PAMAM and dextran aldehyde and composed of gold nanorods and gemcitabine for photothermal therapy and chemotherapy, respectively. It was developed to provide dextran aldehyde-selective adhesion with tissue amines. Since tumor surface expressed high levels of collagen, the exposed amines could act as adhesion points for the gel system. Thus, the gel presented more affinity to tumor tissues. When being instilled, it could form a protective layer on the inner face of the entire bladder wall immediately, preventing RTCs in early time. And it persisted long at the tumor site, ablating RTLs. Our data proved the gel system improved intravesical treatment efficacy in a "divide-and-rule" approach and might be a promising treatment strategy for SI.