2024-03-29T14:50:31Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1313892022-03-24T13:25:27Zcom_10261_5063com_10261_5col_10261_5066
In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles
Nogueira, Daniele Rubert
Tavano, Lorena
Mitjans, Montserrat
Pérez, Lourdes
Infante, María Rosa
Vinardell, María Pilar
Ministerio de Ciencia e Innovación (España)
Chitosan nanoparticles
Cytotoxicity
Intracellular drug delivery
Methotrexate
PH-sensitivity
Lysine-based surfactant
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-CS-NPs 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. © 2013 Elsevier Ltd
2016-04-25T10:15:50Z
2016-04-25T10:15:50Z
2013-04
artículo
Biomaterials
http://hdl.handle.net/10261/131389
10.1016/j.biomaterials.2013.01.005
http://dx.doi.org/10.13039/501100004837
eng
Postprint
http://dx.doi.org/10.1016/j.biomaterials.2013.01.005
Sí
openAccess
Elsevier