Transporte de paclitaxel por nanopartículas de ferrita e quitosana através da avidez por cálcio de células de câncer prostático
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Data
2019-09-16
Autores
Sartori, Sophia Miquelle Ceron Gimenez Ribeiro
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Universidade Estadual Paulista (Unesp)
Resumo
O câncer de próstata é um dos principais tipos de câncer em todo o mundo, sendo o que causa maior morbidade. Apesar da alta probabilidade de cura nos casos com diagnóstico precoce, essa neoplasia é responsável por mais de 80% dos casos de metástases ósseas e, uma vez detectada, a doença maligna é considerada incurável. Os íons de cálcio são fundamentais da maquinaria celular e sua concentração está intimamente ligada a processos vitais, entre eles a proliferação celular. Visto que as células tumorais são mais sensíveis e dependentes dos níveis de cálcio para manutenção da proliferação, apresentando maior avidez por esse elemento que as células normais, no presente estudo testamos a hipótese de que o revestimento, com cálcio (hidroxiapatita), de nanopartículas magnéticas de ferrita Mn-Zn polimerizadas com quitosana, poderia endereçar o fármaco paclitaxel às células de câncer prostático, levando-as à morte celular. Coerente com nossa hipótese inicial, nossos resultados para as nanopartículas mimetizadas com hidroxiapatita mostraram-se com grande potencial citotóxico para células de câncer de próstata LNCaP, sem, entretanto, afetar pró-osteoblastos murinos da linhagem MC3T3. As nanopartículas contendo apenas paclitaxel (bio-NCP-PTX) promoveram níveis de morte celular muito próximos aos observados com concentração similar de PTX puro, apresentando, portanto, resultado superior ao compósito revestido com Ca (bio-NCP-PTX-APA). Por fim, observamos que o núcleo magnético, a matriz polimérica de quitosana revestida ou não com hidroxiapatita, não possuem por si só efeitos tóxicos. Assim, esses resultados indicam que essas nanopartículas têm potencial para carrear quimioterápicos para as células de câncer de próstata.
Prostate cancer figures among the most frequent types of cancer in the world, being the one with greatest morbidity. Despite the high probability of cure of early diagnosed cases, this neoplasm is responsible for more than 80% of cases of bone metastases and, once achieved the disease is considered incurable. Calcium ions are fundamental to the cell machinery and their concentration is closely linked to vital processes, among them cell proliferation. Since tumor cells are more sensitive and dependent on calcium levels to maintain proliferation, being more avid for this element than normal cells, in the present study we tested the hypothesis that mimicryof magnetic MN-Zn nanoparticles polymerized with chitosan, with calcium (hydroxyapatite), would be able to address paclitaxel to prostate cancer cells, leading to cell death. In agreement with our hypothesis, our results show that hydroxyapatite-mimicked nanoparticles have a high cytotoxic potential to LNCaP prostate cancer cells, with no toxicity to non malignant pro-osteoblast murine cell line. Nanoparticles containing only paclitaxel (bio-NCP-PTX) promoted cell death in a level close to that induced by similar concentration of pure paclitaxel. It indicates that this composite worked better than that covered by Ca (bio-NCP-PTX-APA). Finally, we observed that the magnetic core, with the polymer matrix of chitosan coated or not with hydroxyapatite, does not have toxic effects alone. Thus, these results indicate that these nanoparticles are a potencial carrier of drugs for prostate cancer cells.
Prostate cancer figures among the most frequent types of cancer in the world, being the one with greatest morbidity. Despite the high probability of cure of early diagnosed cases, this neoplasm is responsible for more than 80% of cases of bone metastases and, once achieved the disease is considered incurable. Calcium ions are fundamental to the cell machinery and their concentration is closely linked to vital processes, among them cell proliferation. Since tumor cells are more sensitive and dependent on calcium levels to maintain proliferation, being more avid for this element than normal cells, in the present study we tested the hypothesis that mimicryof magnetic MN-Zn nanoparticles polymerized with chitosan, with calcium (hydroxyapatite), would be able to address paclitaxel to prostate cancer cells, leading to cell death. In agreement with our hypothesis, our results show that hydroxyapatite-mimicked nanoparticles have a high cytotoxic potential to LNCaP prostate cancer cells, with no toxicity to non malignant pro-osteoblast murine cell line. Nanoparticles containing only paclitaxel (bio-NCP-PTX) promoted cell death in a level close to that induced by similar concentration of pure paclitaxel. It indicates that this composite worked better than that covered by Ca (bio-NCP-PTX-APA). Finally, we observed that the magnetic core, with the polymer matrix of chitosan coated or not with hydroxyapatite, does not have toxic effects alone. Thus, these results indicate that these nanoparticles are a potencial carrier of drugs for prostate cancer cells.
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Palavras-chave
Próstata - Câncer, Nanopartículas magnéticas, Paclitaxel, Imunologia, Biotecnologia, Ferrita, Quitosana