Banca de DEFESA: JOANA CLAUDIO PIERETTI

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : JOANA CLAUDIO PIERETTI
DATE: 22/05/2025
TIME: 09:00
LOCAL: Auditório 801 no 8º andar do Bloco B do Campus Santo André da Universidade Federal do ABC
TITLE:

IMPACT OF NITRIC OXIDE- AND CHEMOTHERAPEUTIC-BASED NANOPLATFORMS ON CYTOTOXICITY AND SENSITIZATION OF RESISTANT TUMOR CELLS

PAGES: 149
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Físico-Química
SPECIALTY: Química de Interfaces
SUMMARY:

Cancer is one of the leading causes of global mortality, and its treatment faces challenges due to the limitations of conventional therapies and the resistance acquired by tumor cells. Hepatocellular carcinoma (HCC) and prostate cancer are examples of aggressive neoplasms whose patients often have poor prognoses, especially in advanced stages. In this context, nanotechnology emerges as a promising approach to overcome biological barriers and enhance therapeutic efficacy. Among the various types of nanoparticles (NPs), metal oxide NPs, such as zinc oxide (ZnO NPs) and silicon dioxide (SiO₂ NPs), exhibit unique adsorption and biocompatibility properties, making them ideal candidates for developing new therapeutic strategies. Additionally, nitric oxide (NO), an endogenous signaling molecule, has been shown to be an important modulator of cellular responses, potentially sensitizing tumor cells and enhancing the efficacy of chemotherapeutic treatments. In this study, ZnO NPs and SiO₂ NPs were synthesized using hydrothermal and sol-gel methodologies, respectively, and characterized to confirm their physicochemical properties. Subsequently, the cytotoxic effects of these NPs on HCC cells were investigated. While SiO₂ NPs did not exhibit significant toxicity, ZnO NPs demonstrated mitochondrial accumulation, resulting in the inhibition of cellular respiration and the induction of apoptosis in the HepG2 cell line and necroapoptosis in SNU449 cells, indicating significant therapeutic potential. Based on these findings, ZnO NPs were functionalized with cisplatin (ZnO/CisPt NPs) to enable sustained and targeted drug release. ZnO/CisPt NPs exhibited sustained and enhanced release at acidic pH, characteristic of the tumor microenvironment. In prostate cancer (PC3) cells, NO co-therapy potentiated the action of ZnO/CisPt NPs by increasing intracellular S-nitrosothiol (S-NO) concentration and promoting nitrosation processes, leading to a significant reduction in cell viability and greater selectivity compared to normal cells. Furthermore, modulating intracellular NO levels using an NO donor or a nitric oxide synthase inhibitor in combination with ZnO/CisPt NPs in PC3 cells directly impacted NOS expression and inflammatory cytokines, resulting in greater therapeutic efficacy and reduced tumor-associated inflammation. These findings highlight the critical role of NO in improving NP-based therapies, offering a safer and more effective strategy for prostate cancer treatment and opening new perspectives for nanomedicine in oncology. Collectively, these studies demonstrate that the combination of nanomaterials and NO may represent an innovative approach to overcoming tumor resistance and improving cancer therapy efficacy, enabling the development of more targeted strategies and expanding the applications of nanomedicine in oncology.

 

COMMITTEE MEMBERS:
Presidente - Interno ao Programa - 1844792 - AMEDEA BAROZZI SEABRA
Membro Titular - Examinador(a) Interno ao Programa - 2046361 - BRUNO LEMOS BATISTA
Membro Titular - Examinador(a) Externo ao Programa - 1768959 - FERNANDO CARLOS GIACOMELLI
Membro Titular - Examinador(a) Externo ao Programa - 1672728 - ANA CAROLINA SANTOS DE SOUZA GALVAO
Membro Titular - Examinador(a) Externo à Instituição - MARCELO GANZAROLLI DE OLIVEIRA - UNICAMP
Membro Suplente - Examinador(a) Externo ao Programa - 043.750.879-00 - KELLI CRISTINA FREITAS MARIANO - UFABC
Membro Suplente - Examinador(a) Externo à Instituição - Sergio Humberto Domingues
Membro Suplente - Examinador(a) Externo à Instituição - Ademar Benévolo Lugão