Prostate cancer chemotherapy by intratumoral administration of Docetaxel-Mesoporous silica nanomedicines.

Data de publicació: 25/08/2024 Data Ahead of Print: 25/08/2024

Autors de IIS La Fe

• Adrián Bernal Gómez

  Autor

• 

  César David Vera Donoso

  Autor

Autors aliens a IIS La Fe

• Rivero-Buceta, Eva
• Vidaurre-Agut, Carla
• Lopez Moncholi, Eric
• Maria Benlloch, Jose
• Moreno Manzano, Victoria
• Botella, Pablo

Grups d'Investigació

• Núcleo de investigación traslacional integrado Urológico de Valencia (NITIUV)

  

  Leader

  César David Vera Donoso

Abstract

Docetaxel (DTX) is a recommended treatment in patients with metastasic prostate cancer (PCa), despite its therapeutic efficacy is limited by strong systemic toxicity. However, in localized PCa, intratumoral (IT) administration of DTX could be an alternative to consider that may help to overcome the disadvantages of conventional intravenous (IV) therapy. In this context, we here present the first in vivo preclinical study of PCa therapy with nanomedicines of mesoporous silica nanoparticles (MSN) and DTX by IT injection over a xenograft mouse model bearing human prostate adenocarcinoma tumors. The efficacy and tolerability, the biodistribution and the histopathology after therapy have been investigated for the DTX nanomedicine and the free drug, and compared with the IV administration of DTX. The obtained results demonstrate that IT injection of DTX and DTX nanomedicines allows precise and selective therapy of non-metastatic PCa and minimize systemic diffusion of the drug, showing superior activity than IV route. This allows reducing the therapeutic dose by one order and widens substantially the therapeutic window for this drug. Furthermore, the use of DTX nanomedicines as IT injection promotes strong antitumor efficacy and drug accumulation at the tumor site, improving the results obtained with the free drug by the same route.

Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.

Keywords

• Docetaxel; Intratumoral administration; Mesoporous silica nanoparticles; Prostate cancer