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

摘要

The aim of this work is the preparation of an active nanovehicle for the effective administrationudof α-tocopheryl succinate (α-TOS). α-TOS is loaded in the core of nanoparticles (NPs) basedudon amphiphilic pseudo-block copolymers of N-vinyl pyrrolidone and a methacrylic derivative ofudα-TOS. These well-defi ned spherical NPs have sizes below 165 nm and high encapsulation effi -udciencies. In vitro activity of NPs is tested in hypopharynx squamous carcinoma (FaDu) cells andudnonmalignant epithelial cells, demonstrating that the presence of additional α-TOS signifi cantlyudenhances its antiproliferative activity; however, a range of selective concentrations is observed.udThese NPs induce apoptosis of FaDu cells by activating the mitochondria death pathway (viaudcaspase-9). Both loaded and unloaded NPs act via complex II and produce high levels of reactiveudoxygen species that trigger apoptosis. Additionally, theseudNPs effectively suppress the vascular endothelial growth factorud(VEGF) expression of human umbilical vein endothelial cellsud(HUVECs). These results open the possibility to use this promisingudnanoformulation as an α-TOS delivery system for theudeffective cancer treatment, effectively resolving the currentudlimitations of free α-TOS administration.