000087601 001__ 87601
000087601 005__ 20200716101543.0
000087601 0247_ $$2doi$$a10.3390/cancers11121948
000087601 0248_ $$2sideral$$a115815
000087601 037__ $$aART-2019-115815
000087601 041__ $$aeng
000087601 100__ $$0(orcid)0000-0002-8486-8514$$aDe Miguel, Diego
000087601 245__ $$aDouble-edged lipid nanoparticles combining liposome-bound TRAIL and encapsulated doxorubicin showing an extraordinary synergistic pro-apoptotic potential
000087601 260__ $$c2019
000087601 5060_ $$aAccess copy available to the general public$$fUnrestricted
000087601 5203_ $$aAlthough TRAIL (TNF-related apoptosis-inducing ligand, also known as Apo2L) was described as capable of inducing apoptosis in transformed cells while sparing normal cells, limited results obtained in clinical trials has limited its use as an anti-tumor agent. Consequently, novel TRAIL formulations with enhanced bioactivity are necessary for overcoming resistance to conventional soluble TRAIL (sTRAIL) exhibited by many primary tumors. Our group has generated artificial liposomes with sTRAIL anchored on their surface (large unilamellar vesicle (LUV)-TRAIL), which have shown a greater cytotoxic activity both in vitro and in vivo when compared to sTRAIL against distinct hematologic and epithelial carcinoma cells. In this study, we have improved LUV-TRAIL by loading doxorubicin (DOX) in its liposomal lumen (LUVDOX-TRAIL) in order to improve their cytotoxic potential. LUVDOX-TRAIL killed not only to a higher extent, but also with a much faster kinetic than LUV-TRAIL. In addition, the concerted action of the liposomal DOX and TRAIL was specific of the liposomal DOX and was not observed when with soluble DOX. The cytotoxicity induced by LUVDOX-TRAIL was proven to rely on two processes due to different molecular mechanisms: a dynamin-mediated internalization of the doxorubicin-loaded particle, and the strong activation of caspase-8 exerted by the liposomal TRAIL. Finally, greater cytotoxic activity of LUVDOX-TRAIL was also observed in vivo in a tumor xenograft model. Therefore, we developed a novel double-edged nanoparticle combining the cytotoxic potential of DOX and TRAIL, showing an exceptional and remarkable synergistic effect between both agents.
000087601 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/PI16-00526
000087601 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000087601 590__ $$a6.126$$b2019
000087601 591__ $$aONCOLOGY$$b37 / 244 = 0.152$$c2019$$dQ1$$eT1
000087601 592__ $$a1.938$$b2019
000087601 593__ $$aOncology$$c2019$$dQ1
000087601 593__ $$aCancer Research$$c2019$$dQ1
000087601 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000087601 700__ $$aGallego-Lleyda, Ana$$uUniversidad de Zaragoza
000087601 700__ $$aMartinez-Ara, Miguel
000087601 700__ $$0(orcid)0000-0002-4220-105X$$aPlou, Javier
000087601 700__ $$0(orcid)0000-0002-5175-8394$$aAnel, Alberto$$uUniversidad de Zaragoza
000087601 700__ $$0(orcid)0000-0003-3043-147X$$aMartinez-Lostao, Luis$$uUniversidad de Zaragoza
000087601 7102_ $$11008$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Inmunología
000087601 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000087601 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000087601 773__ $$g11, 12 (2019), 1948 [25 pp.]$$pCancers$$tCancers$$x2072-6694
000087601 8564_ $$s4134727$$uhttps://zaguan.unizar.es/record/87601/files/texto_completo.pdf$$yVersión publicada
000087601 8564_ $$s105822$$uhttps://zaguan.unizar.es/record/87601/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000087601 909CO $$ooai:zaguan.unizar.es:87601$$particulos$$pdriver
000087601 951__ $$a2020-07-16-09:41:39
000087601 980__ $$aARTICLE