Chronic exposure to nitric oxide sensitizes prostate cancer cells and improved ZnO/CisPt NPs cytotoxicity and selectivity

Author(s)

Pieretti, Joana Claudio ; Freire, Bruna Moreira ; Armentano, Giovana Marchini ; Santana, Bianca de Melo ; Batista, Bruno Lemos ; Carneiro-Ramos, Marcela Sorelli ; Seabra, Amedea Barozzi

• Document type: Journal article
• Source: International Journal of Pharmaceutics; v. 640, p. 8-pg., 2023-05-10.

Abstract

The co-therapy of common chemotherapeutics with nitric oxide (NO), an endogenous signaling molecule, is proposed as an alternative to sensitize cancer cells and enhance treatments' efficacy. Herein, we have synthesized cisplatin-releasing zinc oxide nanoparticles (ZnO/CisPt NPs), which promoted a sustained and pH targeted release, able to release a higher amount of CisPt at tumor microenvironment conditions. This material was combined with a chronic NO treatment, at low concentration, in prostate cancer cells (PC3). NO treatment enhanced the S-NO concentration in PC3 cells, suggesting the nitrosylation or transnitrosylation processes enhancement, which are directly related to S-NO binding to proteins, function alterations and cancer cells death. Indeed, these mechanisms directly impacted the cytotoxic effect of ZnO/CisPt NPs, inducing a 30 % higher viability reduction of PC3 cells after NO treatment, along with a higher selectivity index when compared to normal human fibroblasts (FN1). (AU)

• FAPESP's process: 22/00321-0 - Nanomaterials combined with nitric oxide donors for biological applications
• Grantee: Amedea Barozzi Seabra
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/03646-2 - Impact of nanoplatforms allied to nitric oxide and chemotherapeutics on cytotoxicity and sensitization of resistant tumor cells
• Grantee: Joana Claudio Pieretti
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 20/08566-7 - Preparation of magnetic nanoparticles of Fe3O4@SiO2 containing nitric oxide for biomedical applications
• Grantee: Bianca de Melo Santana
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 22/00153-0 - Biophotonics applied to study of extracellular vesicles as connectors of kidney-heart crosstalk
• Grantee: Marcela Sorelli Carneiro Ramos
• Support Opportunities: Regular Research Grants