Targeted delivery of atorvastatin by aptamer gated silica nanoparticles in atherosclerosis cell culture model

Cardiovascular diseases (CVD) are the number one cause of deaths all around the world in which atherosclerotic CVD have the biggest portion. Atherosclerosis, known as a chronic inflammation at arterial wall, is caused by endothelial cell (EC) dysfunction which is reported to be induced by low shear stress. In addition, atorvastatin is one of the most commonly used drug in the treatment of atherosclerosis. Targeted delivery of atorvastatin to the atherosclerotic area could increase the efficacy of the drug and minimize the side effects of atorvastatin including adverse muscle events and hepatic dysfunction. Aptamers are single stranded DNA or RNA sequences which have unique tertiary structures that enable them to bind a specific protein of interest. In the present study, aptamers were designed to target intracellular adhesion molecule-1 (ICAM-1) which is an inflammatory marker and increased in atherosclerotic area. In addition, aptamer gated atorvastatin loaded silica nanoparticles (APT-ATS-NP) used in the present study provides controlled release of the atorvastatin. Therefore, the aim of the present study was to research targeted delivery and controlled release of atorvastatin by APT-ATS-NP under normal and low shear stress conditions in the human umbilical vein endothelial cell (HUVECs), which mimics healthy and atherosclerotic conditions, respectively. HUVECs were incubated with different concentrations of atorvastatin which was delivered by APT-ATS-NP under low oscillatory conditions (2.63 dyn/cm2) for 24 hours. In order to evaluate the effects of APT-ATS-NP, intracellular ROS levels were measured by using flow cytometry and protein expression levels of eNOS, Akt, peNOS, pAkt were measured by western blot. Intracellular ROS levels were significantly reduced by 0.1 mM atorvastatin delivery by APT-ATS-NP. Moreover, 5 nM atorvastatin delivery by APT-ATS-NP increased the phosphorylation levels of Akt and eNOS proteins. Therefore, application of aptamer gated nanoparticles in the treatment of atherosclerosis by atorvastatin could be more effective in clinical practices.