Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, China.
Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Shanxi Medical University, Taiyuan, China.
Nanotheranostics. 2023 Apr 2;7(3):327-344. doi: 10.7150/ntno.82654. eCollection 2023.
Atherosclerosis, an inflammation-driven chronic blood vessel disease, is a major contributor to devastating cardiovascular events, bringing serious social and economic burdens. Currently, non-invasive diagnostic and therapeutic techniques in combination with novel nanosized materials as well as established molecular targets are under active investigation to develop integrated molecular imaging approaches, precisely visualizing and/or even effectively reversing early-stage plaques. Besides, mechanistic investigation in the past decades provides many potent candidates extensively involved in the initiation and progression of atherosclerosis. Recent hotly-studied imaging nanoprobes for detecting early plaques mainly including optical nanoprobes, photoacoustic nanoprobes, magnetic resonance nanoprobes, positron emission tomography nanoprobes, and other dual- and multi-modality imaging nanoprobes, have been proven to be surface functionalized with important molecular targets, which occupy tailored physical and biological properties for atherogenesis. Of note, these engineering nanoprobes provide long blood-pool residence and specific molecular targeting, which allows efficient recognition of early-stage atherosclerotic plaques and thereby function as a novel type of precise diagnostic tools as well as potential therapeutic carriers of anti-atherosclerosis drugs. There have been no available nanoprobes applied in the clinics so far, although many newly emerged nanoprobes, as exemplified by aggregation-induced emission nanoprobes and TiO nanoprobes, have been tested for cell lines and atherogenic animal models , achieving good experimental effects. Therefore, there is an urgent call to translate these preclinical results for nanoprobes into clinical trials. For this reason, this review aims to give an overview of currently investigated nanoprobes in the context of atherosclerosis, summarize relevant published studies showing applications of different kinds of formulated nanoprobes in early detection and reverse of plaques, discuss recent advances and some limitations thereof, and provide some insights into the development of the new generation of more precise and efficient molecular nanoprobes, with a critical property of specifically targeting early atherosclerosis.
动脉粥样硬化是一种炎症驱动的慢性血管疾病，是导致灾难性心血管事件的主要原因，给社会和经济带来了严重负担。目前，非侵入性诊断和治疗技术结合新型纳米材料以及已确立的分子靶点，正在积极研究开发综合分子成像方法，精确地可视化和/或甚至有效地逆转早期斑块。此外，过去几十年的机制研究为动脉粥样硬化的发生和发展提供了许多广泛涉及的潜在靶点。最近研究热点的用于检测早期斑块的成像纳米探针主要包括光学纳米探针、光声纳米探针、磁共振纳米探针、正电子发射断层扫描纳米探针和其他双模态和多模态成像纳米探针，已被证明可以表面功能化重要的分子靶点，这些靶点具有针对动脉粥样硬化形成的定制物理和生物学特性。值得注意的是，这些工程纳米探针具有长血液池停留时间和特异性分子靶向性，可以有效识别早期动脉粥样硬化斑块，因此可以作为新型精确诊断工具以及抗动脉粥样硬化药物的潜在治疗载体。目前还没有可用于临床的纳米探针，尽管许多新出现的纳米探针，如聚集诱导发射纳米探针和 TiO2 纳米探针，已经在细胞系和动脉粥样硬化动物模型中进行了测试，取得了良好的实验效果。因此，迫切需要将这些纳米探针的临床前研究结果转化为临床试验。出于这个原因，本综述旨在概述目前在动脉粥样硬化背景下研究的纳米探针，总结不同种类的纳米探针在早期检测和斑块逆转方面的应用的相关已发表研究，讨论其最新进展和一些局限性，并为新一代更精确和有效的分子纳米探针的开发提供一些思路，这些探针具有针对早期动脉粥样硬化的特异性靶向性的关键特性。
