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http://hdl.handle.net/2445/34009
Title: | In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles |
Author: | Nogueira, Daniele R. Tavano, Lorena Mitjans Arnal, Montserrat Pérez Muñoz, Lourdes Infante Martínez-Pardo, Ma. Rosa Vinardell Martínez-Hidalgo, Ma. Pilar |
Keywords: | Agents tensioactius Membranes cel·lulars Nanopartícules Citotoxicitat per mediació cel·lular Nanotoxicologia Surface active agents Cell membranes Nanoparticles Cell-mediated cytotoxicity Nanotoxicology |
Issue Date: | Apr-2013 |
Publisher: | Elsevier B.V. |
Abstract: | Nanoparticles with pH-sensitive behavior may enhance the success of chemotherapy in many cancers by efficient intracellular drug delivery. Here, we investigated the effect of a bioactive surfactant with pH-sensitive properties on the antitumor activity and intracellular behavior of methotrexate-loaded chitosan nanoparticles (MTX-CS-NPs). NPs were prepared using a modified ionotropic complexation process, in which was included the surfactant derived from Nα,Nε-dioctanoyl lysine with an inorganic lithium counterion. The pH-sensitive behavior of NPs allowed accelerated release of MTX in an acidic medium, as well as membrane-lytic pH-dependent activity, which facilitated the cytosolic delivery of endocytosed materials. Moreover, our results clearly proved that MTX-CSNPs were more active against the tumor HeLa and MCF-7 cell lines than the free drug. The feasibilty of using NPs to target acidic tumor extracellular pH was also shown, as cytotoxicity against cancer cells was greater in a mildly acidic environment. Finally, the combined physicochemical and pH-sensitive properties of NPs generally allowed the entrapped drug to induce greater cell cycle arrest and apoptotic effects. Therefore, our overall results suggest that pH-sensitive MTX-CS-NPs could be potentially useful as a carrier system for tumor and intracellular drug delivery in cancer therapy. |
Note: | Versió postprint del document publicat a: http://dx.doi.org/10.1016/j.biomaterials.2013.01.005 |
It is part of: | Biomaterials, 2013, vol. 34, núm. 11, p. 2758-2772 |
URI: | http://hdl.handle.net/2445/34009 |
Related resource: | http://dx.doi.org/10.1016/j.biomaterials.2013.01.005 |
ISSN: | 0142-9612 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Fisiologia) |
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