INVESTIGADORES
LASSALLE Veronica Leticia
congresos y reuniones científicas
Título:
Delivery of doxorubicin from magnetic nanotheranostics: improvement of the antitumoral effect regarding the administration of free drug in colorectal tumor derived cells
Autor/es:
MARIANA JULIA MARTIN; CLAUDIA GENTILI; LASSALLE, VERÓNICA
Reunión:
Congreso; Jornadas Anuales de la Sociedad Argentina de Biología (SAB), XVII Jornadas de la Sociedad Uruguaya de Biociencias (SUB), Segundas Jornadas Rioplatenses de Biología "Nanobiotecnología: Pequeñas soluciones para grandes problemas"; 2018
Resumen:
The incursion of magnetic nanoparticles (MNPs) in the biomedical field has derived in interesting and more efficient tools to resolve traditional problems. The interest is especially centered in the diagnosis and treatment of oncological diseases mediated by the targeted delivery of drugs. The MNPs are, in general, composed of a magnetic core, commonly of iron oxides, modified with different substrates that improve the ?active targeting?. Folic acid (FA), is a widespread molecule used to assess active targeting because of its high affinity for the folate receptors (FR) that are overexpressed on the surface of many human cancer cells, including colorectal cancer (CRC) cells. In statistical terms, CRC is one of the most important causes of morbidity and mortality worldwide and it is the second most frequent type of cancer in Argentina according to the National Cancer Institute. Doxorubicin hydrochloride (DOX) is a broad-spectrum fluorescent antitumor drug for the treatment of CRC and other types of cancer. DOX presents high systemic toxicity, meaning that it is unable to discriminate between cancer and normal cells subjected to rapid division. The targeting of this drug by MNPs could result in an increased bioavailability and a reduction in secondary toxicity. The objective of this work is to provide knowledge about the interactions between the theranostic agent composed of magnetite, FA and DOX and cultures of the cell line derived from CRC, HCT116. The effects on cell viability were evaluated by means of trypan blue dye exclusion test, reveling that the treatment with DOX-Mag for 24 hours significantly decreased the number of living cells with respect to the same doses of free drug. The influence of MAG or FA (in the absence of the drug) on this anti-proliferative effect was ruled out. The effective internalization of MNPs was qualitatively confirmed by staining with Prussian Blue. The quantification of intra and extracellular iron was assessed by absorption atomic spectroscopy by iron determination. In addition, taking advantage of the fluorescence of the DOX molecule, dynamic studies of the release of the drug from DOX-Mag within the cells were performed by fluorescence microscopy. Finally, we purpose that the enzymatic activity over MNPs improved the drug release respect to the values obtained in phosphate buffer at different pH. Taken together, these data suggest that the selectivity given by the FA in the coating of these nanosystems markedly increased the effect of doxorubicin on human CRC models. In this context, this contribution expands the knowledge of the behavior of nanocarriers in contact with in vitro models and proposes the DOX-Mag as a potential theranostic agents for improvement of cancer treatment.