Role of Survivin in Bladder Cancer: Issues to Be Overcome When Designing an Efficient Dual Nano-Therapy

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 f...

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Autores principales:	Maria Arista-Romero, Anna Cascante, Cristina Fornaguera, Salvador Borrós
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	bladder cancer polymeric nanoparticles combined nano-therapies paclitaxel survivin Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/ac3c8783abf7463ebdc2734df51408c8
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spelling	oai:doaj.org-article:ac3c8783abf7463ebdc2734df51408c82021-11-25T18:42:22ZRole of Survivin in Bladder Cancer: Issues to Be Overcome When Designing an Efficient Dual Nano-Therapy10.3390/pharmaceutics131119591999-4923https://doaj.org/article/ac3c8783abf7463ebdc2734df51408c82021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1959https://doaj.org/toc/1999-4923Bladder 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.Maria Arista-RomeroAnna CascanteCristina FornagueraSalvador BorrósMDPI AGarticlebladder cancerpolymeric nanoparticlescombined nano-therapiespaclitaxelsurvivinPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1959, p 1959 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bladder cancer polymeric nanoparticles combined nano-therapies paclitaxel survivin Pharmacy and materia medica RS1-441
spellingShingle	bladder cancer polymeric nanoparticles combined nano-therapies paclitaxel survivin Pharmacy and materia medica RS1-441 Maria Arista-Romero Anna Cascante Cristina Fornaguera Salvador Borrós Role of Survivin in Bladder Cancer: Issues to Be Overcome When Designing an Efficient Dual Nano-Therapy
description	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.
format	article
author	Maria Arista-Romero Anna Cascante Cristina Fornaguera Salvador Borrós
author_facet	Maria Arista-Romero Anna Cascante Cristina Fornaguera Salvador Borrós
author_sort	Maria Arista-Romero
title	Role of Survivin in Bladder Cancer: Issues to Be Overcome When Designing an Efficient Dual Nano-Therapy
title_short	Role of Survivin in Bladder Cancer: Issues to Be Overcome When Designing an Efficient Dual Nano-Therapy
title_full	Role of Survivin in Bladder Cancer: Issues to Be Overcome When Designing an Efficient Dual Nano-Therapy
title_fullStr	Role of Survivin in Bladder Cancer: Issues to Be Overcome When Designing an Efficient Dual Nano-Therapy
title_full_unstemmed	Role of Survivin in Bladder Cancer: Issues to Be Overcome When Designing an Efficient Dual Nano-Therapy
title_sort	role of survivin in bladder cancer: issues to be overcome when designing an efficient dual nano-therapy
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ac3c8783abf7463ebdc2734df51408c8
work_keys_str_mv	AT mariaaristaromero roleofsurvivininbladdercancerissuestobeovercomewhendesigninganefficientdualnanotherapy AT annacascante roleofsurvivininbladdercancerissuestobeovercomewhendesigninganefficientdualnanotherapy AT cristinafornaguera roleofsurvivininbladdercancerissuestobeovercomewhendesigninganefficientdualnanotherapy AT salvadorborros roleofsurvivininbladdercancerissuestobeovercomewhendesigninganefficientdualnanotherapy
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Role of Survivin in Bladder Cancer: Issues to Be Overcome When Designing an Efficient Dual Nano-Therapy

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