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Toxicity and Cellular Uptake of Gold Nanorods in Vascular Endothelium and Smooth Muscles of Isolated Rat Blood Vessel: Importance of Surface Modification

Authors

  • Alaaldin M. Alkilany,

    1. Department of Pharmacology and Toxicology, Georgia Health Sciences University, Augusta, Georgia 30912
    2. Department of Pharmaceutics & Pharmaceutical Technology, Faculty of Pharmacy, University of Jordan, Amman 11942, Jordan
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  • Alia Shatanawi,

    1. Department of Pharmacology and Toxicology, Georgia Health Sciences University, Augusta, Georgia 30912
    2. Department of Pharmacology, Faculty of Medicine, University of Jordan, Amman 11942, Jordan
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  • Timothy Kurtz,

    1. Cell Imaging Laboratory, Georgia Health Sciences University, Augusta, Georgia 30912, USA
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  • Ruth B. Caldwell,

    1. Vascular Biology Center and Department of Cell Biology & Anatomy, Georgia Health Sciences University, Augusta, Georgia 30912, USA
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  • R. William Caldwell

    Corresponding author
    1. Department of Pharmacology and Toxicology, Georgia Health Sciences University, Augusta, Georgia 30912
    • Department of Pharmacology and Toxicology, Georgia Health Sciences University, Augusta, Georgia 30912.
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Abstract

Gold nanorods (GNRs) have promising applications in drug delivery and cancer treatment and are generally administered via direct injection into the circulation. Thus it is necessary to evaluate their potential adverse effects on blood vessels. Herein, GNRs with various surface modifications are used to evaluate the toxicity and cellular uptake of GNRs into vascular endothelial and smooth muscle cells of isolated rat aortic rings. Surfactant-capped GNRs are synthesized and either coated with polyelectrolyte (PE) to prepare PE-GNRs, or modified with thiolated polyethylene glycol (PEG) to prepare PEG-GNRs. Using toxicity assays, small-vessel myography, fluorescence microscopy, and electron microscopy, it is shown that therapeutic concentrations of PE-GNRs but not PEG-GNRs are toxic to the vascular endothelium, which leads to an impaired relaxation function of aortic rings. However, no toxicity to smooth muscles is observed. Moreover, electron microscopy analysis confirms the cellular uptake of PE-GNRs but not PEG-GNRs into the endothelium of exposed aortic rings. The difference in toxicity and cellular uptake of PE-GNRs versus PEG-GNRs is explained and linked to free surfactant molecules and protein adsorption, respectively. The results indicate that toxicity and cellular uptake in the vascular endothelium in blood vessels are potential adverse effects of systemically administered GNR solutions, which can be prevented by appropriate surface functionalization.

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