Nanoparticle-delivered quercetin exhibits enhanced efficacy in eliminating iron-overloaded senescent chondrocytes.
Nanomedicine (Lond)
; : 1-12, 2024 Sep 04.
Article
en En
| MEDLINE
| ID: mdl-39229808
ABSTRACT
Aim:
The therapeutic potential of senolytic drugs in osteoarthritis (OA) is poorly known. Quercetin, a senolytic agent exhibits promising potential to treat OA, having limited bioavailability. We investigated the effects of Quercetin-loaded nanoparticles (Q-NP) with enhanced bioavailability in human chondrocytes mimicking OA phenotype.Materials &methods:
The C-20/A4 chondrocytes were exposed to ferric ammonium citrate to induce OA phenotype, followed by treatment with free Quercetin/Q-NP for 24 and 48-h. Q-NP were synthesized by nanoprecipitation method. Following treatment chondrocytes were assessed for drug cellular bioavailability, viability, cell cycle, apoptosis, oxidative stress and expression of key senescence markers.Results:
Q-NP exhibited 120.1 ± 1.2 nm particle size, 81 ± 2.4% encapsulation efficiency, increased cellular bioavailability and selective apoptosis of senescent chondrocytes compared with free Quercetin. Q-NP treatment also induced oxidative stress and reduced the expressions of senescence markers, including TRB3, p16, p62 and p21 suggesting their ability to eliminate senescent cells. Last, Q-NP arrested the cell cycle in the sub-G0 phase, potentially creating a beneficial environment for tissue repair.Conclusion:
Q-NP propose a promising delivery system for treating OA by eliminating senescent chondrocytes through apoptosis. Furthermore, their enhanced cellular bioavailability and capacity to modify cell cycle and senescent pathways warrant further investigations.
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Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Nanomedicine (Lond)
Año:
2024
Tipo del documento:
Article
País de afiliación:
Emiratos Árabes Unidos