Journal of controlled release : official journal of the Controlled Release SocietyJul 13, 2026

Using Nanoparticles to Remove Aging Cells in Brain Blood Vessels

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jul 14, 2026

Abstract

Polymeric nanoparticles effectively eliminate senescent brain endothelial cells at lower doses than soluble senolytics.

The blood-brain barrier experiences dysfunction during aging, which may lead to cognitive decline.
Brain endothelial cell senescence is identified as a significant factor in blood-brain barrier impairment.
Polymeric nanoparticles loaded with the senolytic agent Navitoclax selectively target and degrade senescent brain endothelial cells.
These nanoparticles restored blood-brain barrier integrity by reducing permeability and diminishing the presence of senescent cells in a rat model.
The nanoparticles improved exploratory behavior in aged rats, indicating potential benefits for cognitive function.

Simplified

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⁺ and p16⁺ BECs in vivo and enhance exploratory behavior. These findings suggest that NPs containing senolytics represent a promising intervention for decreasing BECs senescence, reducing BBB permeability, and enhancing exploratory behavior in naturally aged rats.