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Nanoencapsulated senotherapeutic compounds targeting connexin-43 for enhanced wound healing

Year: 2025
Type: article
Abstract: Oncological patients receiving radiotherapy or chemotherapy often experience impaired wound healing due to tissue damage and cellular senescence. Connexin43 (Cx43) is a key regulator in this process, promoting senescence and the SASP, which hinder regeneration. This study investigates targeting Cx43 in primary dermal fibroblasts from cancer patients using a new combination of nanoencapsulated drugs. We show that Cx43 overexpression correlates with reduced gap junction communication, increased senescence, and delayed healing. Treatment with oleuropein (OLP), a polyphenol with antioxidant and regenerative properties, restores fibroblast function, reduces senescence, and improves healing. We also examine the p38 MAPK inhibitor BIRB796, alone and with OLP, demonstrating its ability to suppress SASP and support tissue repair. After confirming the superior combined effect of OLP and BIRB796, we developed a co-encapsulated nanoformulation. This innovative approach may significantly enhance wound healing in oncological patients.
Source: iScience
DOI: 10.1016/j.isci.2025.114547
Authors: Marina Rodríguez-Candela Mateos, Jenifer García-Fernández, Sofia M. Saraiva, Maria Aurora Grimaudo, Sandra Alijas, Adela Escudero, Marta Varela-Eirín, Juan Pérez Cano, Benigno Acea Nebril, Luis C. Barrio, María D. Mayan, María de la Fuente
Institutions: Complexo Hospitalario Universitario A Coruña, Servicio Gallego de Salud, Instituto de Investigación Biomédica de A Coruña, Complejo Hospitalario Universitario de Santiago, Instituto de Investigación Sanitaria de Santiago, Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón y Cajal, Centro de Investigación Biomédica en Red de Cáncer
Language: English
Subfield: Rehabilitation
Field: Medicine
Open Access status: gold
Estimated APC paid: $3,240
Funders: Ministerio de Ciencia, Innovación y Universidades, European Commission, Consellería de Economía, Emprego e Industria, Xunta de Galicia, Axencia Galega de Innovación, Xunta de Galicia, HORIZON EUROPE Framework Programme, Instituto de Salud Carlos III, European Regional Development Fund, Agencia Estatal de Investigación
Awards: G1033747102, G1990195214, G358895756, G3739821490, G4725840125, G5246954014, Liberación de ARN mensajero al hígado para la producción endógena de biomoléculas con aplicación en inmuno-oncología, G6392100203, G7238325544, G8047245992, G8052220574
OpenAlex ID: W7117308670
FWCI:
Cites: 105
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