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

Abstract

Gold nanorods have promising applications in drug delivery and cancer treatment and are generally administered via direct injection into circulation. Thus it is necessary to evaluation their potential adverse effects on blood vessels. Herein we use gold nanorods with various surface modifications to evaluate the toxicity and cellular uptake of gold nanorods into vascular endothelial and smooth muscle cells of isolated rat aortic rings. Surfactant-capped gold nanorods (GNRs) were synthesized and either: 1) coated with polyelectrolytes (PE) in order to prepare PE-GNRs; or 2) modified with thiolated polyethylene glycol (PEG) in order to prepare PEG-GNRs. Using toxicity assays, small vessel myography, fluorescence microscopy and electron microscopy, we show that therapeutic concentrations of PE-GNRs but not PEG-GNRs are toxic to the vascular endothelium, which leads to impaired relaxation function of aortic rings. However, no toxicity to smooth muscles was observed. Moreover, electron microscopy analysis confirmed the cellular uptake of PE-GNRs but not PEG-GNRs into the endothelium of exposed aortic rings. The difference in toxicity and cellular uptake for PE-GNRs versus PEG-GNRs is explained and linked to free surfactant molecules and protein adsorption, respectively. Our results indicate that toxicity and cellular uptake in vascular endothelium in blood vessels are potential adverse effects of systemically administered gold nanorod solutions, which can be prevented by appropriate surface functionalization.

A histological evaluation and in vivo assessment of intratumoral near infrared photothermal nanotherapy-induced tumor regression

“…Therefore, the inhibited growth pattern observed in the nanorod-only treatment group in our vivo studies is not likely due to any cytotoxicity of the nanorods. 54 It is possible, however, that observed growth inhibition was due to prolonged exposure to ambient light. Elongated NPs like nanorods have two surface plasmon resonance absorption peaks, the longitudinal and transverse modes, corresponding to NIR itself and surrounding, ambient visible light, respectively.…”

Cytotoxicity of CdTe quantum dots in human umbilical vein endothelial cells: the involvement of cellular uptake and induction of pro-apoptotic endoplasmic reticulum stress

“…7 Nonetheless, under some circumstances, the undesirable uptake of toxicants (eg, viruses, bacteria, and some NPs) by ECs can also be observed, and it may result in subsequent organellar or cellular dysfunction. [8][9][10][11] Hence, internalization of heavy metal-based QDs would be expected to alter the activity of cellular organelles of ECs and even these cells per se. Furthermore, ECs also maintain vascular homeostasis through the synthesis and secretion of a variety of vasoactive agents which regulate vasomotor tone, angiogenesis, thrombosis, and atherogenesis.…”

Intravascular photoacoustic imaging of exogenously labeled atherosclerotic plaque through luminal blood

“…This may also be caused by extravasation through an incomplete endothelial layer, as neovasculature associated with atherosclerosis has been shown to exhibit a leaky endothelium. 27 This hypothesis is further supported by recent reports demonstrating that PEG-AUNRs are not endocytosed by endothelial cells following systemic injection, 28 and that injection of indocyanine green, an organic fluorochrome, resulted in a similar pattern of preferential labeling of atherosclerotic plaques. 29 Furthermore, nanoparticles as larger as 250 nm in diameter have been shown to exhibit selective local permeability due to endothelial barrier disruption in a manner which is related to atherosclerotic severity.…”