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dc.contributor.author | Saiz, Maria Laura | |
dc.contributor.author | Lozano-Chamizo, Laura | |
dc.contributor.author | Florez, Aida Bernardo | |
dc.contributor.author | Marciello, Marzia | |
dc.contributor.author | Diaz-Bulnes, Paula | |
dc.contributor.author | Corte-Iglesias, Viviana | |
dc.contributor.author | Bernet, Cristian Ruiz | |
dc.contributor.author | Rodrigues-Diez, Raul R | |
dc.contributor.author | Martin-Martin, Cristina | |
dc.contributor.author | Rodriguez-Santamaria, Mar | |
dc.contributor.author | Fernandez-Vega, Ivan | |
dc.contributor.author | Rodriguez, Ramon M | |
dc.contributor.author | Diaz-Corte, Carmen | |
dc.contributor.author | Suarez-Alvarez, Beatriz | |
dc.contributor.author | Filice, Marco | |
dc.contributor.author | Lopez-Larrea, Carlos | |
dc.date.accessioned | 2024-07-04T10:56:01Z | |
dc.date.available | 2024-07-04T10:56:01Z | |
dc.date.issued | 2024-05 | |
dc.identifier.citation | Biomed Pharmacother. 2024 May:174:116492. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/20070 | |
dc.description.abstract | Targeting epigenetic mechanisms has emerged as a potential therapeutic approach for the treatment of kidney diseases. Specifically, inhibiting the bromodomain and extra-terminal (BET) domain proteins using the small molecule inhibitor JQ1 has shown promise in preclinical models of acute kidney injury (AKI) and chronic kidney disease (CKD). However, its clinical translation faces challenges due to issues with poor pharmacokinetics and side effects. Here, we developed engineered liposomes loaded with JQ1 with the aim of enhancing kidney drug delivery and reducing the required minimum effective dose by leveraging cargo protection. These liposomes efficiently encapsulated JQ1 in both the membrane and core, demonstrating superior therapeutic efficacy compared to freely delivered JQ1 in a mouse model of kidney ischemia-reperfusion injury. JQ1-loaded liposomes (JQ1-NPs) effectively targeted the kidneys and only one administration, one-hour after injury, was enough to decrease the immune cell (neutrophils and monocytes) infiltration to the kidney-an early and pivotal step to prevent damage progression. By inhibiting BRD4, JQ1-NPs suppress the transcription of pro-inflammatory genes, such as cytokines (il-6) and chemokines (ccl2, ccl5). This success not only improved early the kidney function, as evidenced by decreased serum levels of BUN and creatinine in JQ1-NPs-treated mice, along with reduced tissue expression of the damage marker, NGAL, but also halted the production of extracellular matrix proteins (Fsp-1, Fn-1, α-SMA and Col1a1) and the fibrosis development. In summary, this work presents a promising nanotherapeutic strategy for AKI treatment and its progression and provides new insights into renal drug delivery. | es_ES |
dc.description.sponsorship | This study has been funded by Instituto de Salud Carlos III (ISCIII) through the projects No DTS20/00109 (AES20-ISCIII), PI19/00184, PI20/00639, PI22/00738 and PI22/00789 co-funded by the European Union; Adquisicion ´ de equipamiento e Infraestructuras científicot´ecnicas (IFEQ21/00203) and RICORS program to RICORS2040 (Kidney Disease, RD21/0005/0017) funded by European Union with charge to NextGenerationEU that finance the actions of the Mechanism for Recovery and Resilience (MRR)/RETC; PCTI-Plan de Ciencia, Tecnología e Innovacion ´ 2021–2023 del Gobierno del Principado de Asturias/FEDER (Grant number IDI/2021/000032); Sociedad Espanola ˜ de Nefrología SEN 2022, Ayudas a la Investigacion ´ en Nefrología, Proyecto “NANOBET” to B S-A. L.L-C., M.F. and M.M. acknowledge the support of Microscopy & Dynamic Imaging Unit of CNIC, Madrid, Spain. The Unit is part of the ReDiB-ICTS and has the support of FEDER, “Una manera de hacer Europa.” The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovacion ´ (MCIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020–001041-S funded by MICIN/AEI/10.13039/501100011033). Sara Borrell’ program (grant number CD20/00042 to R.R.R.-D.) and Miguel Servet I´program (grant number CP18/00106 to B.S.-A.) from ISCIII. A.B.F (BP20–143) and C.R-B (BP21/044) received a Severo Ochoa Grant from Programa de Ayudas “Severo Ochoa” para la formacion ´ en investigacion ´ y docencia del Principado de Asturias, Gobierno del Principado de Asturias. P.D.-B. has been supported by Red de Investigacion ´ Renal REDINRED, grant number RD21/0005/0017, ISCIII; M.L.S. by FEDER-PCTI 2021–2023, Gobierno del Principado de Asturias (grant number IDI/2021/000032) and R.M.R was supported by a postdoctoral grant from the Scientific Foundation of the Spanish Association Against Cancer (INVES222995RODR). L.L.-C., M.M. and M.F. would like to thank Comunidad de Madrid for the predoctoral grant IND2020/BIO-17523 of L.L.-C. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject.mesh | Azepines | es_ES |
dc.subject.mesh | Reperfusion Injury | es_ES |
dc.subject.mesh | Triazoles | es_ES |
dc.subject.mesh | Renal Insufficiency, Chronic | es_ES |
dc.subject.mesh | Disease Progression | es_ES |
dc.subject.mesh | Mice, Inbred C57BL | es_ES |
dc.subject.mesh | Kidney | es_ES |
dc.subject.mesh | Liposomes | es_ES |
dc.subject.mesh | Bromodomain Containing Proteins | es_ES |
dc.subject.mesh | Nuclear Proteins | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Male | es_ES |
dc.subject.mesh | Transcription Factors | es_ES |
dc.subject.mesh | Acute Kidney Injury | es_ES |
dc.subject.mesh | Disease Models, Animal | es_ES |
dc.subject.mesh | Nanoparticles | es_ES |
dc.subject.mesh | Cell Cycle Proteins | es_ES |
dc.title | BET inhibitor nanotherapy halts kidney damage and reduces chronic kidney disease progression after ischemia-reperfusion injury. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 38537579 | es_ES |
dc.format.volume | 174 | es_ES |
dc.format.page | 116492 | es_ES |
dc.identifier.doi | 10.1016/j.biopha.2024.116492 | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea. NextGenerationEU | es_ES |
dc.contributor.funder | Sociedad Española de Nefrología | es_ES |
dc.contributor.funder | Gobierno del Principado de Asturias (España) | es_ES |
dc.contributor.funder | Comunidad de Madrid (España) | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1950-6007 | es_ES |
dc.relation.publisherversion | 10.1016/j.biopha.2024.116492 | es_ES |
dc.identifier.journal | Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie | es_ES |
dc.repisalud.orgCNIC | CNIC::Unidades técnicas::Microscopía | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/DTS20/00109 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PI19/00184 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PI20/00639 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PI22/00738 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PI22/00789 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/IDI/2021/000032 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/MICIN/AEI/10.13039/501100011033/CEX2020–001041-S | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/CD20/00042 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/CP18/00106 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/RD21/0005/0017 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/IDI/2021/000032 | es_ES |