Endothelium-targeted NF-κB siRNA nanogel for magnetic resonance imaging and visualized-anti-inflammation treatment of atherosclerosis

Atherosclerosis-induced lethal cardiovascular disease remains a severe healthcare threat due to the limited drug efficiency and untimely prediction of high-risk events caused by inadequate target specificity of medications, incapable recognition of insensitive patients, and variable morphology of vu...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Biomaterials 2025-03, Vol.314, p.122897, Article 122897
Hauptverfasser: Guo, Yuanyuan, Wang, Fujun, Wan, Sunli, Liu, Xinhua, Huang, Yu, Xie, Miao, Wei, Xiaoer, Zhu, Wangshu, Yao, Tingting, Li, Yuehua, Zhang, Chuan, Zhu, Yueqi
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Atherosclerosis-induced lethal cardiovascular disease remains a severe healthcare threat due to the limited drug efficiency and untimely prediction of high-risk events caused by inadequate target specificity of medications, incapable recognition of insensitive patients, and variable morphology of vulnerable plaques. Therefore, it is necessary to develop efficient strategies to improve the diagnosis accuracy and achieve visualized treatment of atherosclerosis. Herein, we establish an inflamed endothelium-targeted three-in-one nucleic acid nanogel system that can reverse the inflammatory state of endothelial cells (ECs) in plaques and simultaneously achieve real-time monitoring of the therapy process for efficient atherosclerosis diagnosis and treatment. For this purpose, contrast agent (Gd-DOTA) and VCAM-1-targeted peptide (VP) are first covalently conjugated onto DNA strands by click reaction respectively, which could self-assemble into Y-shaped structures (Gd-Y1 and VP-Y2 motifs) with magnetic resonance (MR) imaging and endothelium targeting capacities. Thereafter, NF-κB subunit p65-targeting siRNA (siNF-κB) is crosslinked with Gd-Y1 and VP-Y2 motifs to construct the endothelium-targeting nanogel platform. With contrast agents inside, the nanogel enables MR-based diagnosis and visualized therapy of atherosclerosis, providing accurate prognostic analysis and indications for treatment results, which ensures timely disclosure of insensitive individuals and avoids acute lethal events. By delivering siNF-κB to inflammatory endothelium, the nanogel significantly regresses plaques in both the aorta and carotid artery with reduced inflammation cytokines, collagens, macrophages, and apoptotic cells, providing a potential anti-inflammation strategy to treat atherosclerosis and avoid acute cardiovascular disease. With contrast agent, peptide, and siNF-κB inside, the as-prepared endothelium-targeted nucleic acid nanogel realizes MR imaging and real-time monitoring of anti-inflammation treatment of atherosclerosis. By targeted functionalizing in inflammatory endothelial cells, the NF-κB nanogel significantly alleviates inflammation and regresses plaques in atherosclerotic mice as characterized by MR imaging and pathological analysis, providing a promising theranostic anti-inflammation strategy for atherosclerosis. [Display omitted] •A facile and efficient nanoplatform with targeting, diagnosis, and therapy capacities.•High diagnosis accuracy and resolution by targetin
ISSN:0142-9612
1878-5905
1878-5905
DOI:10.1016/j.biomaterials.2024.122897