2026-06-03T11:49:16Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/200702024-09-27T08:07:06Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Saiz, Maria Laura
author
Lozano-Chamizo, Laura
author
Florez, Aida Bernardo
author
Marciello, Marzia
author
Diaz-Bulnes, Paula
author
Corte-Iglesias, Viviana
author
Bernet, Cristian Ruiz
author
Rodrigues-Diez, Raul R
author
Martin-Martin, Cristina
author
Rodriguez-Santamaria, Mar
author
Fernandez-Vega, Ivan
author
Rodriguez, Ramon M
author
Diaz-Corte, Carmen
author
Suarez-Alvarez, Beatriz
author
Filice, Marco
author
Lopez-Larrea, Carlos
funder
Instituto de Salud Carlos III
funder
Unión Europea. Comisión Europea. NextGenerationEU
funder
Sociedad Española de Nefrología
funder
Gobierno del Principado de Asturias (España)
funder
Comunidad de Madrid (España)
2024-07-04T10:56:01Z
2024-07-04T10:56:01Z
2024-05
Biomed Pharmacother. 2024 May:174:116492.
10.1016/j.biopha.2024.116492
1950-6007
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
38537579
http://hdl.handle.net/20.500.12105/20070
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.
eng
BET inhibitor nanotherapy halts kidney damage and reduces chronic kidney disease progression after ischemia-reperfusion injury.
journal article
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BET inhibitor nanotherapy halts kidney_Biomed Pharmacother_2024.pdf
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BET inhibitor nanotherapy halts kidney_Biomed Pharmacother_2024.pdf.txt