RESUMO
Antitumor activities have been described in selol, a hydrophobic mixture of molecules containing selenium in their structure, and also in maghemite magnetic nanoparticles (MNPs). Both selol and MNPs were co-encapsulated within poly(lactic-co-glycolic acid) (PLGA) nanocapsules for therapeutic purposes. The PLGA-nanocapsules loaded with MNPs and selol were labeled MSE-NC and characterized by transmission and scanning electron microscopy, electrophoretic mobility, photon correlation spectroscopy, presenting a monodisperse profile, and positive charge. The antitumor effect of MSE-NC was evaluated using normal (MCF-10A) and neoplastic (4T1 and MCF-7) breast cell lines. Nanocapsules containing only MNPs or selol were used as control. MTT assay showed that the cytotoxicity induced by MSE-NC was dose and time dependent. Normal cells were less affected than tumor cells. Cell death occurred mainly by apoptosis. Further exposure of MSE-NC treated neoplastic breast cells to an alternating magnetic field increased the antitumor effect of MSE-NC. It was concluded that selol-loaded magnetic PLGA-nanocapsules (MSE-NC) represent an effective magnetic material platform to promote magnetohyperthermia and thus a potential system for antitumor therapy.
Assuntos
Neoplasias da Mama/terapia , Hipertermia Induzida/métodos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Nanocápsulas/química , Nanocápsulas/uso terapêutico , Compostos de Selênio/administração & dosagem , Animais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Feminino , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Nanocápsulas/ultraestrutura , Resultado do TratamentoRESUMO
Magnetic resonance is used to investigate biodistribution aspects of dextran-coated magnetite nanoparticles (9.4 nm core diameter) in both liver and spleen from 5 minutes up to 6 months after intravenous administration of a magnetic fluid sample in female Swiss mice. Using magnetic resonance data important parameters such as the absorption half-life (t 1/2 = 12 +/- 2 min in the liver and t 1/2 = 11 +/- 2 min in the spleen), the peak time (1.7 +/- 0.2 h in the liver and 1.9 +/- 0.2 h in the spleen), and the disposition half-life of the dextran-coated magnetite nanoparticles in mice organs (t 1/2 = 70 +/- 10 h in the liver and t 1/2 = 32 +/- 7 h in the spleen) were assessed. In addition, light and electron microscopy showed several aspects that may be related to the iron metabolism. Microscopic analysis also revealed that although magnetite nanoparticles or iron released from them are retained in the organism for a long period of time, no morphologic alteration is induced by the intravenous administration of the magnetic fluid sample, evidencing its biocompatibility. The used tests may represent an adequate methodology for nanotoxicology evaluation.
Assuntos
Dextranos/farmacocinética , Portadores de Fármacos/farmacocinética , Nanopartículas de Magnetita/química , Animais , Dextranos/química , Portadores de Fármacos/química , Feminino , Histocitoquímica , Injeções Intravenosas , Fígado/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Microscopia Eletrônica , Modelos Animais , Tamanho da Partícula , Fotomicrografia , Baço/metabolismo , Distribuição TecidualRESUMO
Strong evidence indicates that reactive oxygen species (ROS) play an important role in the initiation as well as the promotion phase of carcinogenesis. Studies support the role of ROS in cancer, in part, by showing that dietary antioxidants act as cancer-preventive agents. Although results are promising, the research on this topic is still controversial. Thus, the aim of this study was to investigate whether vitamins C, E and pequi oil can, individually, provide prevention and/or be used afterward as an adjuvant in cancer therapy. Ehrlich solid tumor-bearing mice received antioxidant as follows: before tumor inoculation, before and after tumor inoculation (continuous administration), and after tumor inoculation; morphometric analyses of tumor, genotoxicity and hematology were then carried out. Antioxidant administrations before tumor inoculation effectively inhibited its growth in the three experimental protocols, but administrations after the tumor's appearance accelerated tumor growth and favored metastases. Continuous administration of pequi oil inhibited the tumor's growth, while the same protocol with vitamins E and C accelerated it, favoring metastasis and increasing oxidative stress on erythrocytes. Except for continuous administration with vitamin E, the development of ascites tumor metastases was linked with increased inflammation. Results suggest that the efficiency and applicability of antioxidants in the medical clinic can depend not only on the nature of the antioxidant, the type and stage of cancer being treated and the prevailing oxygen partial pressure in the tissues, but also on the type of antioxidant therapy chosen.