Nanoparticles as an efficient strategy to eliminate senescent brain endothelial cells.

Inês Tomé, Susana Rosa, David Sanfeliu-Redondo, Francisco Caramelo, Anis Shahzad Khan, Peio Aristu-Zabalza, Maria Grazia Vizioli, Patrícia Pitrez, João Malva, Jordi-Gracia Sancho, Diana Jurk, Vitor Francisco, Lino Ferreira

Center for Neurosciences and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.Center for Neurosciences and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal. · pubmed

Paper

Abstract

The blood-brain barrier (BBB) experiences dysfunction during physiological aging, potentially leading to cognitive decline and the onset of neurodegenerative diseases. Recent research highlights brain endothelial cell (BEC) senescence as a key factor contributing to BBB impairment. In this study, polymeric nanoparticles (NPs) loaded with a senolytic agent - Navitoclax - were designed to selectively eliminate senescent cells more effectively. These NPs are taken up by both proliferative and senescent BECs, but are only degraded in the latter due to the presence of senescence-associated beta-galactosidase (SA-β-gal), releasing the drug to induce cell death. NPs effectively and selectively eliminate senescent BECs at lower doses, without affecting proliferative cells, outperforming the soluble senolytic. NPs were then evaluated in a chronologically aged rat model exhibiting BEC senescence, increased BBB permeability, and diminished exploratory behavior. In comparison to high-dose soluble senolytic, the NPs successfully restored BBB integrity by reducing permeability, diminishing the burden of senescent BECs, and partially improving rat exploratory performance. Notably, only the NPs were able to reduce the presence of p21

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The study demonstrates that polymeric nanoparticles can selectively eliminate senescent brain endothelial cells to restore blood-brain barrier integrity and improve cognitive behavior in aged rats. This research is relevant because it targets cellular senescence, a fundamental hallmark of aging, rather than merely treating downstream symptoms, although the findings are currently limited to preclinical animal models.

Author of this paper? Send a correction.