ABSTRACT
The aim of this work was to develop and test the in vitro biological activity of nanocapsules loaded with a doxorubicin (DOX) free base dissolved in a core of castor oil shelled by poly(methyl vinyl ether-co-maleic anhydride) conjugated to n-octadecylamine residues. This system was stable and monodisperse, with a hydrodynamic diameter of about 300 nm. These nanocapsules changed the intracellular distribution of DOX, from the nuclei to the cytoplasm, and exhibited higher toxicity towards cancer cells - 4T1 and MCF-7 - and significantly lower toxicity towards normal cells - NIH-3T3 and MCF-10A - in vitro. In conclusion, these nanocapsules are suitable DOX carriers, which remain to be studied in in vivo tumor models.
Subject(s)
Breast Neoplasms/drug therapy , Doxorubicin/metabolism , Drug Carriers/chemistry , Nanocapsules/chemistry , Animals , Breast Neoplasms/pathology , Castor Oil , Cell Line , Cell Line, Tumor , Cell Nucleus , Cytoplasm , Doxorubicin/toxicity , Drug Carriers/standards , Humans , MCF-7 Cells , Mice , NIH 3T3 CellsABSTRACT
Due to the low therapeutic index of different chemotherapeutic drugs used for cancer treatment, the development of new anticancer drugs remains an intense field of research. A recently developed mixture of selenitetriacylglycerides, selol, was shown to be active against different cancer cells in vitro. As this compound is highly hydrophobic, it was encapsulated, in a previous study, into poly(methyl vinyl ether-co-maleic anhydride)-shelled nanocapsules in order to improve its dispersibility in aqueous media. Following this line of research, the present report aimed at enhancing the In Vitro activity of the selol nanocapsules against cancerous cells by decorating their surface with folic acid. It is known that several cancer cells overexpress folate receptors. Stable folic acid-decorated selol nanocapsules (SNP-FA) were obtained, which showed to be spherical, with a hydro-dynamic diameter of 364 nm, and zeta potential of -24 mV. In comparison to non-decorated selol nanocapsules, SNP-FA presented higher activity against 4T1, MCF-7 and HeLa cells. Moreover, the decoration of the nanocapsules did not alter their toxicity towards fibroblasts, NIH-3T3 cells. These results show that the decoration with folic acid increased the toxicity of selol nanocapsules to cancer cells. These nanocapsules, besides enabling to disperse selol in an aqueous medium, increased the toxicity of this drug In Vitro, and may be useful to treat cancer in vivo, potentially increasing the specificity of selol towards cancer cells.
