Aiming at early-stage vulnerable plaques: A nanoplatform with dual-mode imaging and lipid-inflammation integrated regulation for atherosclerotic theranostics

• Published in: Bioactive materials Vol. 37; pp. 94 - 105
• Main Authors: Wang, Yao, Chen, Zhebin, Zhu, Qiongjun, Chen, Zhezhe, Fu, Guosheng, Ma, Boxuan, Zhang, Wenbin
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.07.2024; KeAi Publishing Communications Ltd; KeAi Communications Co., Ltd
• Subjects: Acidic oxides; Arteriosclerosis; Astaxanthin; Atherosclerosis; Computed tomography; Contrast agents; Contrast media; Dextran; Dextrans; Dual-mode imaging; Endothelium; Fluorescence; In vivo methods and tests; Inflammation; Lipid-inflammation integrated regulation; Lipids; Medical diagnosis; Medical imaging; Metabolism; Microenvironments; Nanoparticles; Nanoplatform; NF-κB protein; Oxidative stress; Plaques; Precision medicine; Theranostics; Tomography; Transcriptomes; Dual-mode imaging; Lipid-inflammation integrated regulation; Theranostics; Atherosclerosis; Nanoplatform
• ISSN: 2452-199X; 2097-1192; 2452-199X
• DOI: 10.1016/j.bioactmat.2024.03.019

The vulnerable plaques in atherosclerosis can cause severe outcome with great danger of acute cardiovascular events. Thus, timely diagnosis and treatment of vulnerable plaques in early stage can effectively benefit the clinical management of atherosclerosis. In this work, a targeting theranostic strategy on early-stage vulnerable plaques in atherosclerosis is realized by a LAID nanoplatform with X-CT and fluorescent dual-mode imaging and lipid-inflammation integrated regulation abilities. The iodinated contrast agents (ICA), phenylboronic acid modified astaxanthin and oxidized-dextran (oxDEX) jointly construct the nanoparticles loaded with the lipid-specific probe LFP. LAID indicates an active targeting to plaques along with the dual-responsive disassembly in oxidative stress and acidic microenvironment of atherosclerosis. The X-CT signals of ICA execute the location of early-stage plaques, while the LFP combines with lipid cores and realizes the recognition of vulnerable plaques. Meanwhile, the treatment based on astaxanthin is performed for restraining the progression of plaques. Transcriptome sequencing suggests that LAID can inhibit the lipid uptake and block NF-κB pathway, which synergistically demonstrates a lipid-inflammation integrated regulation to suppression the plaques growing. The in vivo investigations suggest that LAID delivers a favorable theranostics to the early-stage vulnerable plaques, which provides an impressive prospect for reducing the adverse prognosis of atherosclerosis. [Display omitted] •A LAID nanoplatform with active targeting ability and dual-responsiveness to ROS and acid environment was constructed.•LAID could actively target to the atherosclerotic plaques mediated by the overexpressed CD44 receptors.•LAID could locate early-stage plaques by X-CT, and achieved lipid-specific fluorescence to recognizing vulnerable plaques.•LAID could inhibit lipid uptake and NF-κB pathway, achieving a lipid-inflammation integrated regulation to atherosclerosis