Chemotactic NO/H<sub>2</sub>S Nanomotors Realizing Cardiac Targeting of G-CSF against Myocardial Ischemia-Reperfusion Injury
Nan Li, Chenxing Huang, Jie Zhang, Junyue Zhang, Jia Huang, Shangshang Li, Xue Xia, Ziyu Wu, Chenglong Chen, Shuwan Tang, Xiangyu Xiao, Hui Gong, Yuxiang Dai, Chun Mao, Mimi Wan
Abstract
Recombinant granulocyte colony-stimulating factor (G-CSF), with a direct repair effect on injured cardiomyocytes against myocardial infarction ischemia-reperfusion-injury (IRI), displays a poor effect owing to the limited cardiac targeting efficacy. There are almost no reports of nanomaterials that deliver G-CSF to the IRI site. Herein, we propose a way to protect G-CSF by constructing one layer of nitric oxide (NO)/hydrogen sulfide (H 2 S) nanomotors on its outside. NO/H 2 S nanomotors with specific chemotactic ability to high expression of reactive oxygen species (ROS)/induced nitric oxide synthase (iNOS) at the IRI site can deliver G-CSF to the IRI site efficiently. Meanwhile, superoxide dismutase is covalently bound to the outermost part, reducing ROS at the IRI site through a cascade effect with NO/H 2 S nanomotors. The synergistic effect between NO and H 2 S on the effective regulation of the IRI microenvironment can not only avoid toxicity caused by excessive concentration of a single gas but also reduce inflammation level and relieve calcium overload, so as to promote G-CSF to play a cardioprotective role.