title: Mitochondrially Targeted Nanoparticles Based on α-TOS for the Selective Cancer Treatment.
abstract: The 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-defined spherical NPs have sizes below 165 nm and high encapsulation efficiencies. 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 significantly 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.
authors.affiliation: Group of Biomaterials, Department of Polymeric Nanomaterials and Biomaterials, Institute of Polymer Science and Technology, CSIC, C/Juan de la Cierva, 3, 28006, Madrid, Spain.|Networking Biomedical Research Centre in Bioengineering, Biomaterials, and Nanomedicine, CIBER-BBN, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Palao-Suay
authors.affiliation: Foundation for Biomedical Research, University Hospital of Getafe, Carretera de Toledo, km 12, 500, 28905, Getafe, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Rodrigáñez
authors.affiliation: Group of Biomaterials, Department of Polymeric Nanomaterials and Biomaterials, Institute of Polymer Science and Technology, CSIC, C/Juan de la Cierva, 3, 28006, Madrid, Spain.|Networking Biomedical Research Centre in Bioengineering, Biomaterials, and Nanomedicine, CIBER-BBN, Spain.
authors.forename: María Rosa
authors.initials: MR
authors.lastname: Aguilar
authors.affiliation: Foundation for Biomedical Research, University Hospital of Getafe, Carretera de Toledo, km 12, 500, 28905, Getafe, Madrid, Spain.|European University of Madrid, C/Tajo s/n. 28670, Villaviciosa de Odón, Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Sánchez-Rodríguez
authors.affiliation: Group of Biomaterials, Department of Polymeric Nanomaterials and Biomaterials, Institute of Polymer Science and Technology, CSIC, C/Juan de la Cierva, 3, 28006, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Parra
authors.affiliation: Group of Biomaterials, Department of Polymeric Nanomaterials and Biomaterials, Institute of Polymer Science and Technology, CSIC, C/Juan de la Cierva, 3, 28006, Madrid, Spain.|Networking Biomedical Research Centre in Bioengineering, Biomaterials, and Nanomedicine, CIBER-BBN, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Fernández
authors.affiliation: Networking Biomedical Research Centre in Bioengineering, Biomaterials, and Nanomedicine, CIBER-BBN, Spain.|Clinical Research and Experimental Biopathology Unit, Healthcare Complex of Ávila, SACYL. C/Jesús del Gran Poder 42, 05003, Ávila, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Parra
authors.affiliation: Foundation for Biomedical Research, University Hospital of Getafe, Carretera de Toledo, km 12, 500, 28905, Getafe, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Riestra-Ayora
authors.affiliation: Foundation for Biomedical Research, University Hospital of Getafe, Carretera de Toledo, km 12, 500, 28905, Getafe, Madrid, Spain.|European University of Madrid, C/Tajo s/n. 28670, Villaviciosa de Odón, Madrid, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Sanz-Fernández
authors.affiliation: Group of Biomaterials, Department of Polymeric Nanomaterials and Biomaterials, Institute of Polymer Science and Technology, CSIC, C/Juan de la Cierva, 3, 28006, Madrid, Spain.|Networking Biomedical Research Centre in Bioengineering, Biomaterials, and Nanomedicine, CIBER-BBN, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: San Román
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053453:Caspase 9 / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009363:Neoplasm Proteins / Q000378:metabolism; D011760:Pyrrolidinones / Q000737:chemistry / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000737:chemistry / Q000494:pharmacology
chemical_list: D009363:Neoplasm Proteins; D011760:Pyrrolidinones; C042670:N-vinyl-2-pyrrolidinone; C506433:CASP9 protein, human; D053453:Caspase 9; D024502:alpha-Tocopherol
keywords: anticancer; apoptosis; nanovehicle; polymer drug; α-tocopheryl succinate