International Journal of Nanomedicine (Oct 2019)
Would Colloidal Gold Nanocarriers Present An Effective Diagnosis Or Treatment For Ischemic Stroke?
Abstract
Hamed Amani,1,2,* Ebrahim Mostafavi,3,* Mahmoud Reza Alebouyeh,4,* Hamidreza Arzaghi,5 Abolfazl Akbarzadeh,6 Hamidreza Pazoki-Toroudi,7 Thomas J Webster3 1Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran; 2Physiology Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran; 3Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 4Anesthesia Department, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran; 5Department of Medical Biotechnology, Faculty of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran; 6Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; 7Physiology Research Center and Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran*These authors contributed equally to this workCorrespondence: Thomas J WebsterDepartment of Chemical Engineering, Northeastern University, Boston, MA, USAEmail [email protected] Pazoki-ToroudiPhysiology Research Center and Department of Physiology, Iran University of Medical Sciences, P.O. Box 14515-763, Tehran, IranFax +98-21-88675760Email [email protected]: This study was conducted to evaluate OX26-PEG-coated gold nanoparticles (GNPs) (OX26@GNPs) as a novel targeted nanoparticulate system on cell survival after ischemic stroke.Materials and methods: Dynamic light scattering (DLS), zeta sizer, and transmission electron microscopy (TEM) were performed to characterize the OX26@GNPs. The effect of OX26@GNPs on infarct volume, neuronal loss, and necroptosis was evaluated 24 h after reperfusion using 2, 3,5-Triphenyltetrazolium chloride (TTC) staining, Nissl staining and Western blot assay, respectively.Results: Conjugation of OX26-PEG to the surface of the 25 nm colloidal gold particles increased their size to 32±2 nm, while a zeta potential change of −40.4 to 3.40 mV remarkably increased the stability of the nanoparticles. Most importantly, OX26@GNPs significantly increased the infarcted brain tissue, while bare GNPs and PEGylated GNPs had no effect on the infarct volume. However, our results indicated an extension of necroptotic cell death, followed by cell membrane damage.Conclusion: Collectively, our results showed that the presently formulated OX26@GNPs are not suitable nanocarriers nor contrast agents under oxidative stress for the diagnosis and treatment of ischemic stroke. Moreover, our findings suggest that the cytotoxicity of GNPs in the brain is significantly associated with their surface charge.Keywords: targeted delivery, gold nanoparticles, necroptosis, surface charge, oxidative stress, cytotoxicity
