TY - JOUR
T1 - Toxicity and cellular uptake of gold nanorods in vascular endothelium and smooth muscles of isolated rat blood vessel
T2 - Importance of surface modification
AU - Alkilany, Alaaldin M.
AU - Shatanawi, Alia
AU - Kurtz, Timothy
AU - Caldwell, Ruth B.
AU - Caldwell, R. William
PY - 2012/4/23
Y1 - 2012/4/23
N2 - 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. Intravascular injection is the main route of nanoparticle administration. Little is known about the potential adverse effects of nanoparticles on blood vessels. Using gold nanorods with different surface chemistry and isolated rat aortic rings, the adverse effects of nanoparticles on blood vessels are evaluated as a function of their surface chemistry.
AB - 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. Intravascular injection is the main route of nanoparticle administration. Little is known about the potential adverse effects of nanoparticles on blood vessels. Using gold nanorods with different surface chemistry and isolated rat aortic rings, the adverse effects of nanoparticles on blood vessels are evaluated as a function of their surface chemistry.
KW - blood vessels
KW - cells
KW - gold
KW - nanorods
KW - toxicity
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U2 - 10.1002/smll.201101948
DO - 10.1002/smll.201101948
M3 - Article
C2 - 22334586
AN - SCOPUS:84859826977
SN - 1613-6810
VL - 8
SP - 1270
EP - 1278
JO - Small
JF - Small
IS - 8
ER -