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

AuthorsPalao-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
Keywordsα-tocopheryl succinate
Polymer drug
Issue Date2016
CitationMacromolecular Bioscience 16 : 395−411 (2016)
AbstractThe 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.
Publisher version (URL)http://dx.doi.org/10.1002/mabi.201500265
Appears in Collections:(ICTP) Artículos
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