Abstract
Bladder cancer is the 10th most diagnosed cancer, with almost 10 M cancer deaths last year worldwide. Currently, chemotherapy is widely used as adjuvant therapy after surgical transurethral resection. Paclitaxel (PTX) is one of the most promising drugs, but cancer cells acquire resistance, causing failure of this treatment and increasing the recurrence of the disease. This poor chemotherapeutic response has been associated with the overexpression of the protein survivin. In this work, we present a novel dual nano-treatment for bladder cancer based on the hypothesis that the inhibition of survivin in cancer cells, using a siRNA gene therapy strategy, could decrease their resistance to PTX. For this purpose, two different polymeric nanoparticles were developed to encapsulate PTX and survivin siRNA independently. PTX nanoparticles showed sizes around 150 nm, with a paclitaxel loading of around 1.5%, that produced sustained tumor cell death. In parallel, siRNA nanoparticles, with similar sizes and loading efficiency of around 100%, achieved the oligonucleotide transfection and knocking down of survivin expression that also resulted in tumor cell death. However, dual treatment did not show the synergistic effect expected. The root cause of this issue was found to be the cell cycle arrest produced by nuclear survivin silencing, which is incompatible with PTX action. Therefore, we concluded that although the vastly reported role of survivin in bladder cancer, its silencing does not sensitize cells to currently applied chemotherapies.
Highlights
The most common histologic type of bladder cancer is urothelial carcinoma, which was formerly known as transitional cell carcinoma (TCC), due to the fact that the transitional cells located at the outside layer of the bladder are the ones transformed into cancer cells [3]
Protein Bromelain (PB), poly (beta aminoesters and polymer P were synthesized by other group members, as previously detailed [16,22,23,27]. small interfering RNA (siRNA) non-targeting pool was obtained from Dharmacon (D-001 206-13-05) (GE Healthcare, CO, USA) and siRNA-F AF 546 was obtained from
Survivin is attracting great attraction as one of the most relevant. It is an inhibitor of apoptosis protein (IAP) involved in many cellular responses to stress, presented in different subcellular compartments
Summary
Bladder cancer is the 10th most diagnosed cancer with an estimated 440,000 new cases worldwide in 2020, accounting for a 5-year prevalence of up to 1.7 M people [1,2]. The most common histologic type of bladder cancer is urothelial carcinoma, which was formerly known as transitional cell carcinoma (TCC), due to the fact that the transitional cells located at the outside layer of the bladder are the ones transformed into cancer cells [3]. 75% of patients are non-muscle-invasive TCC and have a 5-year survival rate between 88% and 98% [2,6]. The other 25% of patients diagnosed with TCC are muscle-invasive in stages between 1 and 4
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
