Detalhes bibliográficos
| Ano de defesa: |
2023 |
| Autor(a) principal: |
Pohl, Ariane Ribas |
| Orientador(a): |
Rech , Virginia Cielo |
| Banca de defesa: |
Vaucher , Rodrigo de Almeida,
Schuck, Patrícia Fernanda,
Vizzotto, Bruno Stefanello,
da Silva, William Leonardo |
| Tipo de documento: |
Tese
|
| Tipo de acesso: |
Acesso aberto |
| Idioma: |
por |
| Instituição de defesa: |
Universidade Franciscana
|
| Programa de Pós-Graduação: |
Programa de Pós-Graduação em Nanociências
|
| Departamento: |
Biociências e Nanomateriais
|
| País: |
Brasil
|
| Palavras-chave em Português: |
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| Palavras-chave em Inglês: |
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| Área do conhecimento CNPq: |
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| Link de acesso: |
http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/1197
|
Resumo: |
Melanoma is the most aggressive form of skin cancer, being a highly malignant neoplasm that affects melanocytes, representing less than 5% of all cases of skin cancer, however, it causes the vast majority of deaths, reaching 80%. Overall, historically survival has been low for patients with metastatic disease and response to conventional chemotherapy has been infrequent. Due to the large number of people affected, the severity and mortality of this disease, innovative methods such as nanostructures with plant compounds may become an alternative for the treatment of cancer. Among the bioactives, quercetin and curcumin stand out, with high antioxidant and anti inflammatory power, and capsaicin, which favors the uptake of curcumin after oral ingestion. However, these natural actives have low aqueous solubility, a characteristic that makes it difficult to use them in clinical trials, and low oral bioavailability, indicating a low use of bioactives. To overcome these problems, incorporating bioactives into solid lipid nanoparticles (NLS) or nanostructured lipid composites (CLN) may allow for more efficient delivery. In this context, the objective of this study is to evaluate the effect of both, the solid lipid nanoparticle containing curcumin and capsaicin (NCC), and the nanostructured lipid carrier containing quercetin (NQ) in B16-F10 melanoma cells, in in vitro and in vitro assays. alive. The cytotoxic potentials of the nanoformulations were determined by the MTT, LDH, Neutral Red, Crystal Violet, Picogreen and hemolysis tests. All concentrations of NCC and NQ reduced melanoma cell viability by the MTT, Neutral Red, and Crystal Violet test. There was greater binding to DNA in the NCC group in the Picogreen test, showing DNA extravasation from the intracellular to the extracellular environment visualized by the double-stranded intercalator. There was a dose-dependent increase in cell death for both nanostructures in the LDH test. There was a reduction in DCFH oxidation, an indication that the antioxidant power of NCC and NQ reduced reactive oxygen species in these groups when compared to the control group. The nanoformulations did not cause hemolysis. Curcumin exhibited concentration-dependent anticoagulant activity, and the NBC and NQ groups did not affect the extrinsic coagulation cascade. For NCC and NBQ they were higher than the accepted range, showing that the anticoagulant action of curcumin in prolonging the clotting time may be due to the hydrophobic groups of its structure. In in vivo tests, treatments with NCC and NQ nanostructures significantly decreased the tumor growth rate over the 21 days of the experiment, and tumor volume was significantly inhibited by approximately 76% (0.23 mm3) and 68 % (0.3 mm3) after treatment with NCC and NQ, respectively, and tumor weight was significantly inhibited from 58% (0.71 g) and 32% (1.15 g) in NCC and NQ groups, respectively, when compared to the melanoma group (1.68 g). In the cytokine test, there was a reduction in IL-17 values in the NQ and NCC groups compared to the melanoma group, indicating the possibility of decreased tumor growth, and a decrease in IL-6 values in the group treated with NQ and NCC, decreasing thus the proliferation of tumor cells. For TNF-α, there was a reduction in the melanoma group and an increase in the NQ and NCC groups, suggesting induction of apoptosis and necrosis of tumor cells. The reduction in IL-10 values corroborates the histology results that did not find signs of metastasis in the lung. Reduction in IL-2 in the NQ and NCC groups, indicating a reduction in the proliferation of cancer cells. The results obtained in the hemogram corroborate what was found in the histology, and in the histology test, where there was no metastasis to the lung. These previous results demonstrate the ability of NCC and NQ to reduce B16-F10 melanoma cells. This thesis is original and innovative, because for the first time NLS containing curcumin and capsaicin, and CLN containing quercetin in melanoma were tested. |
