Division of Cardiovascular Medicine, Frankel Cardiovascular Center , University of Michigan , Ann Arbor , Michigan 48109 , United States.
Section of Cardiology , Ann Arbor Veterans Health System , Ann Arbor , Michigan 48109 , United States.
ACS Nano. 2020 Feb 25;14(2):1236-1242. doi: 10.1021/acsnano.0c00245. Epub 2020 Jan 27.
The past several decades have brought significant advances in the application of clinical and preclinical nanoparticulate drugs in the field of cancer, but nanodrug development in cardiovascular disease has lagged in comparison. Improved understanding of the spatiotemporal kinetics of nanoparticle delivery to atherosclerotic plaques is required to optimize preclinical nanodrug delivery and to drive their clinical translation. Mechanistic studies using super-resolution and correlative light microscopy/electron microscopy permit a broad, ultra-high-resolution picture of how endothelial barrier integrity impacts the enhanced permeation and retention (EPR) effect for nanoparticles as a function of both atherosclerosis progression and metabolic therapy. Studies by Beldman in the December issue of suggest atherosclerotic plaque progression supports endothelial junction stabilization, which can reduce nanoparticle entry into plaques, and metabolic therapy may induce similar effects. Herein, we examine the potential for advanced dynamic intravital microscopy-based mechanistic studies of nanoparticle entry into atherosclerotic plaques to shed light on the advantages of free extravasation immune-mediated nanoparticle uptake for effective clinical translation. We further explore the potential combination of metabolic therapy with another emerging cardiovascular disease treatment paradigm-efferocytosis stimulation-to enhance atherosclerotic plaque regression.
过去几十年，临床和临床前纳米颗粒药物在癌症领域的应用取得了重大进展，但与癌症相比，心血管疾病的纳米药物发展相对滞后。为了优化临床前纳米药物的输送并推动其临床转化，需要更好地了解纳米颗粒向动脉粥样硬化斑块输送的时空动力学。使用超分辨率和相关的荧光显微镜/电子显微镜进行的机制研究，为内皮屏障完整性如何影响纳米颗粒的增强渗透和保留（EPR）效应提供了广泛的超高分辨率图片，这种效应与动脉粥样硬化进展和代谢治疗有关。Beldman 在 12 月的一期中进行的研究表明，动脉粥样硬化斑块的进展支持内皮连接的稳定，这可以减少纳米颗粒进入斑块，而代谢治疗可能会产生类似的效果。在此，我们研究了基于先进的动态活体显微镜的纳米颗粒进入动脉粥样硬化斑块的机制研究的潜力，以阐明自由外渗免疫介导的纳米颗粒摄取对有效临床转化的优势。我们进一步探讨了代谢治疗与另一种新兴的心血管疾病治疗模式——噬斑细胞刺激的联合应用，以增强动脉粥样硬化斑块的消退。
