Tabish Tanveer A, Crabtree Mark J, Townley Helen E, Winyard Paul G, Lygate Craig A
Division of Cardiovascular Medicine, Radcliffe Department of Medicine, British Heart Foundation (BHF) Centre of Research Excellence, University of Oxford, Oxford, United Kingdom.
Department of Biochemical Sciences, School of Biosciences & Medicine, University of Surrey, Guildford, United Kingdom.
JACC Basic Transl Sci. 2023 Oct 18;9(5):691-709. doi: 10.1016/j.jacbts.2023.07.017. eCollection 2024 May.
A central paradigm of cardiovascular homeostasis is that impaired nitric oxide (NO) bioavailability results in a wide array of cardiovascular dysfunction including incompetent endothelium-dependent vasodilatation, thrombosis, vascular inflammation, and proliferation of the intima. Over the course of more than a century, NO donating formulations such as organic nitrates and nitrites have remained a cornerstone of treatment for patients with cardiovascular diseases. These donors primarily produce NO in the circulation and are not targeted to specific (sub)cellular sites of action. However, safe, and therapeutic levels of NO require delivery of the right amount to a precise location at the right time. To achieve these aims, several recent strategies aimed at therapeutically generating or releasing NO in living systems have shown that polymeric and inorganic (silica, gold) nanoparticles and nanoscale metal-organic frameworks could either generate NO endogenously by the catalytic decomposition of endogenous NO substrates or can store and release therapeutically relevant amounts of NO gas. NO-releasing nanomaterials have been developed for vascular implants (such as stents and grafts) to target atherosclerosis, hypertension, myocardial ischemia-reperfusion injury, and cardiac tissue engineering. In this review, we discuss the advances in design and development of novel NO-releasing nanomaterials for cardiovascular therapeutics and critically examine the therapeutic potential of these nanoplatforms to modulate cellular metabolism, to regulate vascular tone, inhibit platelet aggregation, and limit proliferation of vascular smooth muscle with minimal toxic effects.
心血管稳态的一个核心范式是，一氧化氮（NO）生物利用度受损会导致一系列心血管功能障碍，包括内皮依赖性血管舒张功能不全、血栓形成、血管炎症以及内膜增生。在一个多世纪的时间里，诸如有机硝酸盐和亚硝酸盐等供NO制剂一直是心血管疾病患者治疗的基石。这些供体主要在循环系统中产生NO，并非靶向特定的（亚）细胞作用位点。然而，安全且具有治疗效果的NO水平需要在正确的时间将适量的NO输送到精确的位置。为实现这些目标，最近一些旨在在生物系统中治疗性生成或释放NO的策略表明，聚合物和无机（二氧化硅、金）纳米颗粒以及纳米级金属有机框架能够通过内源性NO底物的催化分解内源性生成NO，或者能够储存和释放治疗相关量的NO气体。已开发出用于血管植入物（如支架和移植物）的NO释放纳米材料，以靶向动脉粥样硬化、高血压、心肌缺血再灌注损伤和心脏组织工程。在本综述中，我们讨论了用于心血管治疗的新型NO释放纳米材料在设计和开发方面的进展，并批判性地审视了这些纳米平台在调节细胞代谢、调节血管张力、抑制血小板聚集以及限制血管平滑肌增殖且毒性最小化方面的治疗潜力。
