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| Author(s): |
Gabriella Sales Calaço Roque
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ/SBD) |
| Defense date: | 2023-07-27 |
| Examining board members: |
Ana Olívia de Souza;
Silas Granato Villas Boas;
Maria Gabriela Berzoti Coelho;
Durvanei Augusto Maria;
Fabio Rodrigues
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| Advisor: | Ana Olívia de Souza |
| Abstract | |
Data from the literature show promising antitumor properties of silver nanoparticles (AgNPs) of biological origin that represent a new alternative for the treatment of cancer. With this perspective, in this study, seven mycogenic AgNPs were obtained using the fungal species Aspergillus tubingensis (AgNP-AT), Aspergillus spp. (AgNP-Asp), Bionectria ochroleuca (AgNP-BO), Cladosporium pini-ponderosae (AgNP-CPP), Fusarium proliferatum (AgNP-FP), Epicoccum nigrum (AgNP-EN) e Exserohilum rostratum (AgNP-ER). The AgNPs were characterized by dynamic light scattering (DLS), polydispersion index (PDI), Zeta potential (PZ), transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR) and showed spherical shape and size from 21.8 to 35.8 nm. Cytotoxicity of AgNPs was evaluated in breast cancer cells (MCF-7 and MDA-MB-231), pancreas cancer cells (MIA PaCa-2), and normal human fibroblast cells (FN1) by MTT (3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay at times of 24, 48, and 72 h. The values of concentrations effective in inhibiting 50% of cell proliferation in tumor cells were defined as corresponding to IC50 and in normal cells as CC50. In 48 h, AgNP-BO, AgNP-AT, and AgNP-Asp demonstrated high cytotoxicity for MDA-MB-231 cells, with IC50 of 0.0016; 0.0025; and 0.0253 mM, respectively, while showing low cytotoxicity for FN1 cells, with a CC50 of 0.0982; 0.2130, and 1.3190. IC50 and CC50 values were used to calculate the AgNPs selectivity index (SI = CC50/IC50) in 48 h, being 85.20; 61.38 and 52.13 for AgNP-AT, AgNP-BO and AgNP-Asp, indicating the specificity of AgNPs for tumor cells. Considering the high specificity of AgNP-AT for MDA-MB-231 cells, its action was also evaluated in the cell cycle phases, cell proliferation, induction of apoptosis and mutagenicity. At 0.03 mM, AgNP-AT induced cell cycle arrest in the S phase, a 1.7-fold increase in apoptosis and no damage to the chromosomes of V79-4 cells. The data confirm the cytotoxicity and specificity of AgNP-AT for MDA-MB-231 tumor cells, with an IS of 85.20, indicating low toxicity for normal cells. (AU) | |
| FAPESP's process: | 20/04799-7 - Study of antitumor activity of biogenic silver nanoparticles |
| Grantee: | Gabriella Sales Calaço Roque |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |