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
This study reports on the successful use of magnetic albumin nanosphere (MAN), consisting of maghemite nanoparticles hosted by albumin-based nanosphere, to target different sites within the central nervous system (CNS). Ultrastructural analysis by transmission electron microscopy (TEM) of the material collected from the mice was performed in the time window of 30 minutes up to 30 days after administration. Evidence found that the administered MAN was initially internalized and transported by erythrocytes across the blood-brain-barrier and transferred to glial cells and neuropils before internalization by neurons, mainly in the cerebellum. We hypothesize that the efficiency of MAN in crossing the BBB with no pathological alterations is due to the synergistic effect of its two main components, the iron-based nanosized particles and the hosting albumin-based nanospheres. We found that the MAN in targeting the CNS represents an important step towards the design of nanosized materials for clinical and diagnostic applications.
Assuntos
Fármacos do Sistema Nervoso Central/química , Nanopartículas de Magnetita/química , Nanocompostos/química , Soroalbumina Bovina/química , Animais , Células Sanguíneas/química , Células Sanguíneas/citologia , Encéfalo/citologia , Encéfalo/metabolismo , Encéfalo/ultraestrutura , Química Encefálica , Bovinos , Fármacos do Sistema Nervoso Central/administração & dosagem , Fármacos do Sistema Nervoso Central/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Histocitoquímica , Nanopartículas de Magnetita/administração & dosagem , Camundongos , Microscopia Eletrônica de Transmissão , Nanocompostos/administração & dosagem , Tamanho da Partícula , Soroalbumina Bovina/administração & dosagem , Soroalbumina Bovina/farmacocinética , Distribuição TecidualRESUMO
BACKGROUND: The magnetic albumin nanosphere (MAN), encapsulating maghemite nanoparticles, was designed as a magnetic drug delivery system (MDDS) able to perform a variety of biomedical applications. It is noteworthy that MAN was efficient in treating Ehrlich's tumors by the magnetohyperthermia procedure. METHODS AND MATERIALS: In this study, several nanotoxicity tests were systematically carried out in mice from 30 minutes until 30 days after MAN injection to investigate their biocompatibility status. Cytometry analysis, viability tests, micronucleus assay, and histological analysis were performed. RESULTS: Cytometry analysis and viability tests revealed MAN promotes only slight and temporary alterations in the frequency of both leukocyte populations and viable peritoneal cells, respectively. Micronucleus assay showed absolutely no genotoxicity or cytotoxicity effects and histological analysis showed no alterations or even nanoparticle clusters in several investigated organs but, interestingly, revealed the presence of MAN clusters in the central nervous system (CNS). CONCLUSION: The results showed that MAN has desirable in vivo biocompatibility, presenting potential for use as a MDDS, especially in CNS disease therapy.
Assuntos
Materiais Biocompatíveis/toxicidade , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas de Magnetita/toxicidade , Soroalbumina Bovina/toxicidade , Análise de Variância , Animais , Química Encefálica/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Citometria de Fluxo , Histocitoquímica , Contagem de Leucócitos , Leucócitos/efeitos dos fármacos , Teste de Materiais , Camundongos , Testes para Micronúcleos , Nanosferas/toxicidade , Testes de ToxicidadeRESUMO
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.