Key Lab of Synthetic and Biological Colloids, Ministry of Education, State Key Lab of Food Science and Technology, International Joint Research Laboratory for Biointerface and Biodetection, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, P. R. China.
Angew Chem Int Ed Engl. 2020 May 25;59(22):8698-8705. doi: 10.1002/anie.202002576. Epub 2020 Mar 17.
Cellular senescence is stress-induced, irreversible growth arrest, and is thought to impair tissue function. The clearance of senescent cells can delay the features of senescence. Herein, we report the development of plasmonic core-shell spiky nanorods (CSNRs) surface-modified with an anti-beta-2-microglobulin (aB2MG) antibody and triphenylphosphonium (TPP), to target the mitochondria in senescent cells. aB2MG-TPP@CSNRs irradiated with near-infrared (NIR) light selectively caused mitochondrial damage and apoptosis of senescent cells with relatively low NIR light power, and the ability of CSNRs to activate and amplify the immune response in vitro and in vivo was discovered. The photo-induced generation of reactive oxygen species (ROS) resulted in senescent-cell apoptosis and immune adjuvant effect by CSNRs accelerated the clearance of senescent cells in mice. This study opens the way for the use of precisely regulated plasmonic nanostructures for immune adjuvant and photo-induced apoptosis for age-related senescence.
细胞衰老(Cellular senescence)是一种应激诱导的、不可逆的生长停滞状态,被认为会损害组织功能。清除衰老细胞(senescent cells)可以延缓衰老的特征。在此,我们报告了一种等离子核壳刺状纳米棒(plasmonic core-shell spiky nanorods,CSNRs)的发展,该纳米棒表面修饰有抗β-2-微球蛋白(anti-beta-2-microglobulin,aB2MG)抗体和三苯基膦(triphenylphosphonium,TPP),以靶向衰老细胞(senescent cells)的线粒体。用近红外(near-infrared,NIR)光照射带负电荷的 aB2MG-TPP@CSNRs 可以选择性地导致衰老细胞的线粒体损伤和细胞凋亡,而相对较低的 NIR 光功率就能实现这一效果,并且还发现 CSNRs 具有在体外和体内激活和放大免疫反应的能力。光诱导产生的活性氧(reactive oxygen species,ROS)通过 CSNRs 导致衰老细胞凋亡和免疫佐剂效应,从而加速了小鼠体内衰老细胞的清除。这项研究为使用精确调控的等离子体纳米结构进行免疫佐剂和光诱导凋亡以治疗与年龄相关的衰老开辟了道路。