A Dual-Targeting, Multi-Faceted Biocompatible Nanodrug Optimizes the Microenvironment to Ameliorate Abdominal Aortic Aneurysm

A Dual-Targeting, Multi-Faceted Biocompatible Nanodrug Optimizes the Microenvironment to Ameliorate Abdominal Aortic Aneurysm

© 2024 Wiley‐VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 33 vom: 15. Aug., Seite e2405761
1. Verfasser: Mo, Fandi (VerfasserIn)
Weitere Verfasser: Wang, Chufan, Li, Shiyi, Li, Zheyun, Xiao, Cheng, Zhang, Yuchong, Hu, Chengkai, Wang, Enci, Lin, Peng, Yuan, Tong, Zuo, Ziang, Fu, Weiguo, Chen, Xiaoyuan, Ren, Lei, Wang, Lixin
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2024
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article abdominal aortic aneurysm autophagy macrophage polarization single cell RNA sequencing smooth muscle cell dysfunction virus‐like nanocage Biocompatible Materials Everolimus 9HW64Q8G6G mehr... Integrin alphaVbeta3 Oligopeptides
Beschreibung
Zusammenfassung:© 2024 Wiley‐VCH GmbH.
Abdominal aortic aneurysm (AAA) is a highly lethal cardiovascular disease that currently lacks effective pharmacological treatment given the complex pathophysiology of the disease. Here, single-cell RNA-sequencing data from patients with AAA and a mouse model are analyzed, which reveals pivotal pathological changes, including the M1-like polarization of macrophages and the loss of contractile function in smooth muscle cells (SMCs). Both cell types express the integrin αvβ3, allowing for their dual targeting with a single rationally designed molecule. To this end, a biocompatible nanodrug, which is termed EVMSR-HNC, that consists of the multifunctional drug everolimus (EVMS) encapsulated by the hepatitis B virus core protein modifies to contain the RGD sequence to specifically bind to integrin αvβ3 is designed. Both in vitro and in vivo results show that EVMS@R-HNC can target macrophages as well as SMCs. Upon binding of the nanodrug, the EVMS is released intracellularly where it exhibits multiple functions, including inhibiting M1 macrophage polarization, thereby suppressing the self-propagating inflammatory cascade and immune microenvironment imbalance, while preserving the normal contractile function of SMCs. Collectively, these results suggest that EVMS@R-HNC presents a highly promising therapeutic approach for the management of AAA
Beschreibung:Date Completed 15.08.2024
Date Revised 15.08.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.202405761