000126912 001__ 126912
000126912 005__ 20241125101132.0
000126912 0247_ $$2doi$$a10.1021/acsnano.3c01599
000126912 0248_ $$2sideral$$a134462
000126912 037__ $$aART-2023-134462
000126912 041__ $$aeng
000126912 100__ $$aTorres-Herrero, B.
000126912 245__ $$aRemote activation of enzyme nanohybrids for cancer prodrug therapy controlled by magnetic heating
000126912 260__ $$c2023
000126912 5060_ $$aAccess copy available to the general public$$fUnrestricted
000126912 5203_ $$aHerein, we have developed nanohybrids (nHs) to remotely activate a therapeutic enzyme for its use in Directed Enzyme Prodrug Therapy (DEPT). The coencapsulation of magnetic nanoparticles (MNPs) with horseradish peroxidase (HRP) using biomimetic silica as an entrapment matrix was optimized to obtain nanosized hybrids (∼150 nm) for remote activation of the therapeutic enzyme. HRP converts indole-3-acetic acid (3IAA) into peroxylated radicals, whereas MNPs respond to alternating magnetic fields (AMFs) becoming local hotspots. The AMF application triggered an increase in the bioconversion rate of HRP matching the activity displayed at the optimal temperature of the nHs (Topt = 50 °C) without altering the temperature of the reaction media. This showed that enzyme nanoactuation is possible with MNPs even if they are not covalently bound. After an extensive physicochemical/magnetic characterization, the spatial location of each component of the nH was deciphered, and an insulating role of the silica matrix was suggested as critical for introducing remote control over HRP. In vitro assays, using a human pancreatic cancer cell line (MIA PaCa-2), showed that only upon exposure to AMF and in the presence of the prodrug, the enzyme-loaded nHs triggered cell death. Moreover, in vivo experiments showed higher reductions in the tumor volume growth in those animals treated with nHs in the presence of 3IAA when exposed to AMF. Thus, this work demonstrates the feasibility of developing a spatiotemporally controlled DEPT strategy to overcome unwanted off-target effects.
000126912 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E15-20R$$9info:eu-repo/grantAgreement/EC/H2020/829162/EU/Redesigning biocatalysis: Thermal-tuning of one-pot multienzymatic cascades by nanoactuation/HOTZYMES$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 829162-HOTZYMES$$9info:eu-repo/grantAgreement/ES/ISCIII/CB16-01/00263$$9info:eu-repo/grantAgreement/ES/MCIU/FPU19-01311$$9info:eu-repo/grantAgreement/ES/MICINN/PID2020-118485RB-I00
000126912 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000126912 590__ $$a15.8$$b2023
000126912 592__ $$a4.593$$b2023
000126912 591__ $$aCHEMISTRY, PHYSICAL$$b14 / 178 = 0.079$$c2023$$dQ1$$eT1
000126912 593__ $$aEngineering (miscellaneous)$$c2023$$dQ1
000126912 591__ $$aNANOSCIENCE & NANOTECHNOLOGY$$b11 / 141 = 0.078$$c2023$$dQ1$$eT1
000126912 593__ $$aPhysics and Astronomy (miscellaneous)$$c2023$$dQ1
000126912 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b15 / 231 = 0.065$$c2023$$dQ1$$eT1
000126912 593__ $$aNanoscience and Nanotechnology$$c2023$$dQ1
000126912 591__ $$aMATERIALS SCIENCE, MULTIDISCIPLINARY$$b27 / 439 = 0.062$$c2023$$dQ1$$eT1
000126912 593__ $$aMaterials Science (miscellaneous)$$c2023$$dQ1
000126912 594__ $$a26.0$$b2023
000126912 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000126912 700__ $$0(orcid)0000-0002-2854-2907$$aArmenia, I.
000126912 700__ $$0(orcid)0000-0002-4261-9480$$aAlleva, M.
000126912 700__ $$0(orcid)0000-0003-0641-3407$$aAsín, L.
000126912 700__ $$aCorrea, S.
000126912 700__ $$aOrtiz, C.
000126912 700__ $$0(orcid)0000-0002-0970-1917$$aFernández-Afonso, Y.
000126912 700__ $$0(orcid)0000-0003-2366-3598$$aGutiérrez, L.$$uUniversidad de Zaragoza
000126912 700__ $$0(orcid)0000-0003-1081-8482$$aMartínez De la Fuente, J.
000126912 700__ $$aBetancor, L.
000126912 700__ $$0(orcid)0000-0001-6170-4237$$aGrazú, V.
000126912 7102_ $$12009$$2750$$aUniversidad de Zaragoza$$bDpto. Química Analítica$$cÁrea Química Analítica
000126912 773__ $$g17, 13 (2023), 12358-12373$$pACS Nano$$tACS NANO$$x1936-0851
000126912 8564_ $$s8502196$$uhttps://zaguan.unizar.es/record/126912/files/texto_completo.pdf$$yVersión publicada
000126912 8564_ $$s3068304$$uhttps://zaguan.unizar.es/record/126912/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000126912 909CO $$ooai:zaguan.unizar.es:126912$$particulos$$pdriver
000126912 951__ $$a2024-11-22-11:59:22
000126912 980__ $$aARTICLE