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2013-04

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/34009

In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles

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http://dx.doi.org/10.1016/j.biomaterials.2013.01.005

Resum

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.

Matèries

Agents tensioactius, Membranes cel·lulars, Nanopartícules, Citotoxicitat per mediació cel·lular, Nanotoxicologia

Matèries (anglès)

Surface active agents, Cell membranes, Nanoparticles, Cell-mediated cytotoxicity, Nanotoxicology

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Articles publicats en revistes (Bioquímica i Fisiologia)

Citació

NOGUEIRA, Daniele R., et al. In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles. Biomaterials. 2013. Vol. 34, num. 11, pags. 2758-2772. ISSN 0142-9612. [consulted: 22 of May of 2026]. Available at: https://hdl.handle.net/2445/34009

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