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Role of survivin in bladder cancer: issues to overcome when designing effective dual nanotherapy

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Pharmaceutical. 2021 November 19; 13 (11): 1959. doi: 10.3390 / pharmaceutics13111959.

ABSTRACT

Bladder cancer is the 10th most diagnosed cancer, with nearly 10 million cancer deaths last year worldwide. Currently, chemotherapy is widely used as an adjuvant treatment after transurethral surgical resection. One of the most promising drugs is paclitaxel (PTX), but cancer cells develop resistance, causing treatment to fail and increasing recurrence of the disease. This poor chemotherapeutic response has been associated with overexpression of the survivin protein. In this work, we present a novel dual nanotreatment for bladder cancer based on the hypothesis that inhibition of survivin in cancer cells, using an siRNA gene therapy strategy, could decrease their resistance to bladder cancer. PTX. To this end, two different polymer nanoparticles have been developed to independently encapsulate PTX and survivin siRNA. The PTX nanoparticles showed sizes of around 150 nm, with a paclitaxel load of around 1.5%, which produced lasting tumor cell death. In parallel, siRNA nanoparticles, with similar sizes and approximately 100% loading efficiency, enabled the transfection of oligonucleotides and suppression of survivin expression, which also resulted in cell death. tumor. However, the double treatment did not show the expected synergistic effect. The root cause of this problem was found to be cell cycle arrest produced by the quenching of nuclear survivin, which is incompatible with the action of PTX. Therefore, we concluded that although survivin’s widely reported role in bladder cancer, its silence does not sensitize cells to currently applied chemotherapies.

PMID:34834374 | DO I:10.3390 / pharmaceutical13111959


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