{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T07:42:01Z","timestamp":1772782921117,"version":"3.50.1"},"reference-count":89,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,12,3]],"date-time":"2015-12-03T00:00:00Z","timestamp":1449100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2015,12,3]],"date-time":"2015-12-03T00:00:00Z","timestamp":1449100800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2015,12,3]],"date-time":"2015-12-03T00:00:00Z","timestamp":1449100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Spanish Ministry of Economy and Competitiveness","award":["MAT2010-18155"],"award-info":[{"award-number":["MAT2010-18155"]}]},{"name":"CIBER BBN-ECO Foundation project"},{"name":"European University of Madrid"}],"content-domain":{"domain":["wiley.com"],"crossmark-restriction":true},"short-container-title":["Macromolecular Bioscience"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:p>The aim of this work is the preparation of an active nanovehicle for the effective administration of \u03b1\u2010tocopheryl succinate (\u03b1\u2010TOS). \u03b1\u2010TOS is loaded in the core of nanoparticles (NPs) based on amphiphilic pseudo\u2010block copolymers of N\u2010vinyl pyrrolidone and a methacrylic derivative of \u03b1\u2010TOS. These well\u2010defined 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 \u03b1\u2010TOS 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\u20109). 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 \u03b1\u2010TOS delivery system for the effective cancer treatment, effectively resolving the current limitations of free \u03b1\u2010TOS administration.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/mabi201500265-abs-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1002\/mabi.201500265","type":"journal-article","created":{"date-parts":[[2015,12,3]],"date-time":"2015-12-03T11:36:54Z","timestamp":1449142614000},"page":"395-411","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Mitochondrially Targeted Nanoparticles Based on \u03b1\u2010TOS for the Selective Cancer Treatment"],"prefix":"10.1002","volume":"16","author":[{"given":"Raquel","family":"Palao\u2010Suay","sequence":"first","affiliation":[{"name":"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"},{"name":"Networking Biomedical Research Centre in Bioengineering, Biomaterials, and Nanomedicine CIBER\u2010BBN  Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Rodrig\u00e1\u00f1ez","sequence":"additional","affiliation":[{"name":"Foundation for Biomedical Research University Hospital of Getafe  Carretera de Toledo, km 12, 500 28905 Getafe Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Rosa","family":"Aguilar","sequence":"additional","affiliation":[{"name":"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"},{"name":"Networking Biomedical Research Centre in Bioengineering, Biomaterials, and Nanomedicine CIBER\u2010BBN  Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"S\u00e1nchez\u2010Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Foundation for Biomedical Research University Hospital of Getafe  Carretera de Toledo, km 12, 500 28905 Getafe Madrid Spain"},{"name":"European University of Madrid C\/Tajo s\/n. 28670  Villaviciosa de Od\u00f3n Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Parra","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"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"},{"name":"Networking Biomedical Research Centre in Bioengineering, Biomaterials, and Nanomedicine CIBER\u2010BBN  Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Parra","sequence":"additional","affiliation":[{"name":"Networking Biomedical Research Centre in Bioengineering, Biomaterials, and Nanomedicine CIBER\u2010BBN  Spain"},{"name":"Clinical Research and Experimental Biopathology Unit Healthcare Complex of \u00c1vila SACYL. C\/Jes\u00fas del Gran Poder 42  05003 \u00c1vila Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Riestra\u2010Ayora","sequence":"additional","affiliation":[{"name":"Foundation for Biomedical Research University Hospital of Getafe  Carretera de Toledo, km 12, 500 28905 Getafe Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Sanz\u2010Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Foundation for Biomedical Research University Hospital of Getafe  Carretera de Toledo, km 12, 500 28905 Getafe Madrid Spain"},{"name":"European University of Madrid C\/Tajo s\/n. 28670  Villaviciosa de Od\u00f3n Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julio San","family":"Rom\u00e1n","sequence":"additional","affiliation":[{"name":"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"},{"name":"Networking Biomedical Research Centre in Bioengineering, Biomaterials, and Nanomedicine CIBER\u2010BBN  Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,12,3]]},"reference":[{"key":"e_1_2_6_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2011.02.012"},{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.21022"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.05.2308"},{"key":"e_1_2_6_4_1","first-page":"83\/489","volume-title":"Mayo Clinic Proceedings","author":"Marur S.","year":"2008"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.10-3-215"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032641"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032646"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2012.09.033"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2012.08.042"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2011.05.507"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-1441"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2008.11.010"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/bc100070g"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2010.03.011"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2004.07.027"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1147"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.123.3191.309"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161211798764933"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3365"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-394625-6.00008-8"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2010.05.001"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.05.072"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-006-9060-z"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2007.02.003"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201100066"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2012.09.009"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2012.10.015"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.5732\/cjc.008.10182"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/07315724.2003.10719283"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.2000.1559"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2015.04.003"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1166\/jbt.2013.1076"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2014.03.009"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.22002"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2012.05.031"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.5b00130"},{"key":"e_1_2_6_37_1","first-page":"6674","volume":"62","author":"Cuezva J. M.","year":"2002","journal-title":"Cancer Res."},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5173(89)90281-0"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009093200"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704184"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2010.139"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2012.12.006"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp800051m"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3tb20296h"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2009.11.002"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.20833"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-3034"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2010.02.008"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.07.100"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2013.11.002"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2013.09.007"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2013.10.002"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajd.12025"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp400007k"},{"key":"e_1_2_6_55_1","first-page":"699","volume":"80","author":"Liao C.","year":"2011","journal-title":"Eur. J. Radiol."},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-010-0087-2"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.08.051"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.49.1.407"},{"key":"e_1_2_6_59_1","first-page":"29\/15","volume-title":"Seminars in Oncology","author":"Folkman J.","year":"2002"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2006.06.014"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2004.09.011"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-290-2_7"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2005.05.014"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp060121r"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp900191s"},{"key":"e_1_2_6_66_1","first-page":"2758","volume":"21","author":"Zhou X. X.","year":"2012","journal-title":"Chin. J. New Drugs"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2312"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.57.2.6"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/35011084"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1150"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R800084200"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202581"},{"key":"e_1_2_6_73_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065X.2003.00048.x"},{"key":"e_1_2_6_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2009.09.004"},{"key":"e_1_2_6_75_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200208089"},{"key":"e_1_2_6_76_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a008656"},{"key":"e_1_2_6_77_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.47.120505.105110"},{"key":"e_1_2_6_78_1","first-page":"222","volume":"70","author":"Ross M.","year":"2005","journal-title":"Biochemistry"},{"key":"e_1_2_6_79_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20080063"},{"key":"e_1_2_6_80_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501527200"},{"key":"e_1_2_6_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.69"},{"key":"e_1_2_6_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.110"},{"key":"e_1_2_6_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2008.11.009"},{"key":"e_1_2_6_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2010.06.004"},{"key":"e_1_2_6_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1910"},{"key":"e_1_2_6_86_1","doi-asserted-by":"publisher","DOI":"10.2741\/2322"},{"key":"e_1_2_6_87_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161210789941838"},{"key":"e_1_2_6_88_1","first-page":"3819","volume":"27","author":"Bradburn J. E.","year":"2007","journal-title":"Anticancer Res."},{"key":"e_1_2_6_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2006.02.013"}],"container-title":["Macromolecular Bioscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmabi.201500265","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmabi.201500265","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mabi.201500265","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T05:00:18Z","timestamp":1696395618000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mabi.201500265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,3]]},"references-count":89,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["10.1002\/mabi.201500265"],"URL":"https:\/\/doi.org\/10.1002\/mabi.201500265","archive":["Portico"],"relation":{},"ISSN":["1616-5187","1616-5195"],"issn-type":[{"value":"1616-5187","type":"print"},{"value":"1616-5195","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,3]]}}}