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Development of graphene oxide hybrids as platform for the treatment of non-invasive bladder cancer: interactions of Bacillus Calmette-Gueri immunotherapy, metformin and RNA interference

Funder: São Paulo Research Foundation

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The most widely used therapy modality for the treatment of bladder cancer (BC) is based on the intravesical administration of Bacillus Calmette-Gueri (BCG) associated with transurethral resection. The anti-tumor effects of BCG start by triggering a systemic immune response involving both humoral and cellular components through the activation of Toll-like receptors (TLR) agonists, providing anti-tumor and anti-angiogenic activity. Despite the anti-cancer activity of BCG, a significant number of patients undergoing this treatment have shown intolerance, besides potentially fatal complications, such as systemic BCG infection. Furthermore, 50 % of non-muscle invasive BC (BCNMI) tumors have recurrence within 4 years after treatment and 11 % of the cases present invasive phenotype. Metformin is a drug used in the treatment of type II diabetes. Several studies demonstrate that metformin has anti cancer activity involving different mechanisms, among them aspects concerning the cellular metabolism. Besides metformin, after the recent discovery of interference RNA (siRNA), these substances started to be studied by silencing genes associated with cancer. In this project, we aim to develop graphene oxide (GO) hybrids for simultaneous administration of metformin and siRNA for VEGF (vascular endothelial growth factor). Furthermore, we propose the association between GO hybrids containing metformin and siRNA and the conventional therapy with BCG. It is expected that such associations potentiate the anti-cancer activity compared to the administration of metformin and siRNA alone and in relation to the usual therapy with BCG. For that, the GO will be chemically modified for entrapment of those molecules. The hybrids will be characterized by physical and chemical methods such as atomic force microscopy (AFM), infrared absorption spectroscopy (FTIR), determination of zeta potential and particle size. The complexation of siRNA by GO will be evaluated by electrophoresis. The in vitro cell transfection will also be evaluated and the VEGF expression will be quantified by ELISA. Ultimately, the hybrids which provide better physicochemical properties, lower cytotoxicity and higher silencing activity under VEGF production will be investigated in vivo to determine the antitumor activity against BCNMI. (AU)
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    1112 Oncology and Carcinogenesis

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  • RCDC

    Urologic Diseases



  • Health Research Areas


  • Broad Research Areas

    Clinical Medicine and Science