Belcastro Eugenia, Rehman Asad Ur, Remila Lamia, Park Sin-Hee, Gong Dal Seong, Anton Nicolas, Auger Cyril, Lefebvre Olivier, Goetz Jacky G, Collot Mayeul, Klymchenko Andrey S, Vandamme Thierry F, Schini-Kerth Valérie B
INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine, Faculty of Pharmacy.
University of Strasbourg, CNRS, CAMB UMR 7199, Strasbourg, France.
Nanomedicine. 2021 Jun;34:102379. doi: 10.1016/j.nano.2021.102379. Epub 2021 Mar 11.
Endothelial senescence has been identified as an early event in the development of endothelial dysfunction, a hallmark of cardiovascular disease. This study developed theranostic nanocarriers (NC) decorated with VCAM-1 antibodies (NC-VCAM-1) in order to target cell surface VCAM-1, which is overexpressed in senescent endothelial cells (ECs) for diagnostic and therapeutic purposes. Incubation of Ang II-induced premature senescent ECs or replicative senescent ECs with NC-VCAM-1 loaded with lipophilic fluorescent dyes showed higher fluorescence signals than healthy EC, which was dependent on the NC size and VCAM-1 antibodies concentration, and not observed following masking of VCAM-1. NC loaded with omega 3 polyunsaturated fatty acid (NC-EPA:DHA6:1) were more effective than native EPA:DHA 6:1 to prevent Ang II-induced VCAM-1 and p53 upregulation, and SA-β-galactosidase activity in coronary artery segments. These theranostic NC might be of interest to evaluate the extent and localization of endothelial senescence and to prevent pro-senescent endothelial responses.
内皮细胞衰老已被确定为内皮功能障碍发展过程中的早期事件，而内皮功能障碍是心血管疾病的一个标志。本研究开发了用血管细胞黏附分子-1（VCAM-1）抗体修饰的诊疗纳米载体（NC）（NC-VCAM-1），以靶向细胞表面的VCAM-1，该分子在衰老的内皮细胞（EC）中过表达，用于诊断和治疗目的。用负载亲脂性荧光染料的NC-VCAM-1孵育血管紧张素II诱导的早衰内皮细胞或复制性衰老内皮细胞，其荧光信号高于健康内皮细胞，这取决于NC的大小和VCAM-1抗体浓度，而在VCAM-1被封闭后未观察到这种现象。负载ω-3多不饱和脂肪酸的NC（NC-EPA:DHA6:1）比天然的EPA:DHA 6:1更有效地预防血管紧张素II诱导的VCAM-1和p53上调，以及冠状动脉节段中的衰老相关β-半乳糖苷酶活性。这些诊疗NC可能有助于评估内皮细胞衰老的程度和定位，并预防促衰老的内皮反应。
