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Mitochondrially targeted nanoparticles for the selective treatment of Head and Neck Squamous Cell Carcinoma

AutorPalao-Suay, Raquel; Rodrigáñez, Laura; Aguilar, María Rosa ; Sánchez-Rodríguez, Carolina; Parra, Francisco ; Fernández, Mar; Parra, Juan ; Riestra-Ayora, Juan; Sanz-Fernández, Ricardo; San Román, Julio
Palabras claveα-tocopheryl succinate
Anticancer
Apoptosis
Nanovehicle
Polymer drug
Fecha de publicación2016
EditorWiley-VCH
CitaciónMacromolecular Bioscience 16 : 395−411 (2016)
ResumenThe aim of this work is the preparation of an active nanovehicle for the effective administration of α-tocopheryl succinate (α-TOS). α-TOS is loaded in the core of nanoparticles (NPs) based on amphiphilic pseudo-block copolymers of N-vinyl pyrrolidone and a methacrylic derivative of α-TOS. These well-defi ned spherical NPs have sizes below 165 nm and high encapsulation effi - ciencies. In vitro activity of NPs is tested in hypopharynx squamous carcinoma (FaDu) cells and nonmalignant epithelial cells, demonstrating that the presence of additional α-TOS signifi cantly enhances its antiproliferative activity; however, a range of selective concentrations is observed. These NPs induce apoptosis of FaDu cells by activating the mitochondria death pathway (via caspase-9). Both loaded and unloaded NPs act via complex II and produce high levels of reactive oxygen species that trigger apoptosis. Additionally, these NPs effectively suppress the vascular endothelial growth factor (VEGF) expression of human umbilical vein endothelial cells (HUVECs). These results open the possibility to use this promising nanoformulation as an α-TOS delivery system for the effective cancer treatment, effectively resolving the current limitations of free α-TOS administration.
Versión del editorhttp://dx.doi.org/10.1002/mabi.201500265
URIhttp://hdl.handle.net/10261/139787
DOI10.1002/mabi.201500265
ISSN1616-5187
E-ISSN1616-5195
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