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

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.

Journal of controlled release : official journal of the Controlled Release Society. 2018 Jul 02 [Epub]

Pengyu Guo, Wenting Shang, Li Peng, Lu Wang, Hongzhi Wang, Ziyu Han, Hongmei Jiang, Jie Tian, Kun Wang, Wanhai Xu

Urology Surgery Department, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, PR China; CAS Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, PR China; University of Chinese Academy of Sciences, Beijing 100080, PR China; Heilongjiang Key Laboratory of Scientific Research in Urology, Harbin, Heilongjiang 150001, PR China., Urology Surgery Department, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, PR China; Heilongjiang Key Laboratory of Scientific Research in Urology, Harbin, Heilongjiang 150001, PR China., CAS Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, PR China; University of Chinese Academy of Sciences, Beijing 100080, PR China., CAS Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, PR China; University of Chinese Academy of Sciences, Beijing 100080, PR China. Electronic address: ., CAS Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, PR China; University of Chinese Academy of Sciences, Beijing 100080, PR China. Electronic address: ., Urology Surgery Department, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, PR China; Heilongjiang Key Laboratory of Scientific Research in Urology, Harbin, Heilongjiang 150001, PR China. Electronic address: .