Targeted elimination of senescent cells by engineered extracellular vesicles attenuates atherosclerosis in ApoE^-/- mice with minimal side effects.

ABSTRACT: Senescent cells in plaques emerge as a detrimental factor for atherosclerosis (AS), for which targeted senolysis might be a promising therapeutic strategy. The development of safe and efficient senolytics for senescent cell eradication by targeted delivery is greatly needed. Methods: Pro-apoptotic intelligent Bax (iBax)-overexpressing plasmid was constructed by molecular cloning, in which Bax CDS was fused to miR-122 recognition sites. Extracellular vesicle-based senolytics (EV^iTx) were developed to be conjugated with magnetic nanoparticles on the surface, iBax mRNA encapsulated inside, and BAX activator BTSA1 incorporated into the membrane. EV^iTx was characterized, and in vivo distribution was tracked via fluorescence

SUBMITTER: Zhang L 

PROVIDER: S-EPMC10526664 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature