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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
Author(s) -
Alkilany Alaaldin M.,
Shatanawi Alia,
Kurtz Timothy,
Caldwell Ruth B.,
Caldwell R. William
Publication year - 2012
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201101948
Subject(s) - endothelium , nanorod , blood vessel , surface modification , toxicity , biophysics , materials science , vascular smooth muscle , nanotechnology , chemistry , medicine , biology , smooth muscle
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.