Integrated Cascade Nanozymes with Antisenescence Activities for Atherosclerosis Therapy.
Angew Chem Int Ed Engl
; 62(33): e202304465, 2023 08 14.
Article
en En
| MEDLINE
| ID: mdl-37338457
ABSTRACT
Senescent cells are the critical drivers of atherosclerosis formation and maturation. Mitigating senescent cells holds promise for the treatment of atherosclerosis. In an atherosclerotic plaque microenvironment, senescent cells interact with reactive oxygen species (ROS), promoting the disease development. Here, we hypothesize that a cascade nanozyme with antisenescence and antioxidant activities can serve as an effective therapeutic for atherosclerosis. An integrated cascade nanozyme with superoxide dismutase- and glutathione peroxidase-like activities, named MSe1 , is developed in this work. The obtained cascade nanozyme can attenuate human umbilical vein endothelial cell (HUVEC) senescence by protecting DNA from damage. It significantly weakens inflammation in macrophages and HUVECs by eliminating overproduced intracellular ROS. Additionally, the MSe1 nanozyme effectively inhibits foam cell formation in macrophages and HUVECs by decreasing the internalization of oxidized low-density lipoprotein. After intravenous administration, the MSe1 nanozyme significantly inhibits the formation of atherosclerosis in apolipoprotein E-deficient (ApoE-/- ) mice by reducing oxidative stress and inflammation and then decreases the infiltration of inflammatory cells and senescent cells in atherosclerotic plaques. This study not only provides a cascade nanozyme but also suggests that the combination of antisenescence and antioxidative stress holds considerable promise for treating atherosclerosis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Aterosclerosis
/
Placa Aterosclerótica
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2023
Tipo del documento:
Article
País de afiliación:
China