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Evolocumab loaded Bio-Liposomes for efficient atherosclerosis therapy

PCSK9, which is closely related to atherosclerosis, is significantly expressed in vascular smooth muscle cells (VSMCs). Moreover, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) mediated phenotypic transformation, abnormal proliferation, and migration of VSMCs play key roles in accelerating at...

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Detalles Bibliográficos
Autores principales: Li, Zhenxian, Zhu, Haimei, Liu, Hao, Liu, Dayue, Liu, Jianhe, Jiang, Jiazheng, Zhang, Yi, Qin, Zhang, Xu, Yijia, Peng, Yuan, Liu, Bin, Long, Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10199622/
https://www.ncbi.nlm.nih.gov/pubmed/37208681
http://dx.doi.org/10.1186/s12951-023-01904-4
Descripción
Sumario:PCSK9, which is closely related to atherosclerosis, is significantly expressed in vascular smooth muscle cells (VSMCs). Moreover, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) mediated phenotypic transformation, abnormal proliferation, and migration of VSMCs play key roles in accelerating atherosclerosis. In this study, by utilizing the significant advantages of nano-materials, a biomimetic nanoliposome loading with Evolocumab (Evol), a PCSK9 inhibitor, was designed to alleviate atherosclerosis. In vitro results showed that (Lipo + M)@E NPs up-regulated the levels of α-SMA and Vimentin, while inhibiting the expression of OPN, which finally result in the inhibition of the phenotypic transition, excessive proliferation, and migration of VSMCs. In addition, the long circulation, excellent targeting, and accumulation performance of (Lipo + M)@E NPs significantly decreased the expression of PCSK9 in serum and VSMCs within the plaque of ApoE(−/−) mice. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-023-01904-4.