Polyvinylpyrrolidone-coated gold nanoparticles inhibit endothelial cell viability, proliferation, and ERK1/2 phosphorylation and reduce the magnitude of endothelial-independent dilator responses in isolated aortic vessels.

BACKGROUND: Gold nanoparticles (AuNPs) demonstrate clinical potential for drug delivery and imaging diagnostics. As AuNPs aggregate in physiological fluids, polymer-surface modifications are utilized to allow their stabilization and enhance their retention time in blood. However, the impact of AuNPs on blood vessel function remains poorly understood. In the present study, we investigated the effects of AuNPs and their stabilizers on endothelial cell (EC) and vasodilator function. MATERIALS AND METHODS: Citrate-stabilized AuNPs (12±3 nm) were synthesized and surface-modified using mercapto polyethylene glycol (mPEG) and polyvinylpyrrolidone (PVP) polymers. Their uptake by isolated ECs and whole vessels was visualized using transmission electron microscopy and quantified using inductively coupled plasma mass spectrometry. Their biological effects on EC proliferation, viability, apoptosis, and the ERK1/2-signaling pathway were determined using automated cell counting, flow cytometry, and Western blotting, respectively. Endothelial-dependent and independent vasodilator functions were assessed using isolated murine aortic vessel rings ex vivo. RESULTS: AuNPs were located in endothelial endosomes within 30 minutes' exposure, while their surface modification delayed this cellular uptake over time. After 24 hours' exposure, all AuNPs (including polymer-modified AuNPs) induced apoptosis and decreased cell viability/proliferation. These inhibitory effects were lost after 48 hours' exposure (except for the PVP-modified AuNPs). Furthermore, all AuNPs decreased acetylcholine (ACh)-induced phosphorylation of ERK1/2, a key signaling protein of cell function. mPEG-modified AuNPs had lower cytostatic effects than PVP-modified AuNPs. Citrate-stabilized AuNPs did not alter endothelial-dependent vasodilation induced by ACh, but attenuated endothelial-independent responses induced by sodium nitroprusside. PVP-modified AuNPs attenuated ACh-induced dilation, whereas mPEG-modified AuNPs did not, though this was dose-related. CONCLUSION: We demonstrated that mPEG-modified AuNPs at a therapeutic dosage showed lower cytostatic effects and were less detrimental to vasodilator function than PVP-modified AuNPs, indicating greater potential as agents for diagnostic imaging and therapy.

Biocompatibility of amorphous silica nanoparticles: Size and charge effect on vascular function, in vitro.

Synthetic amorphous silica is gaining popularity as the material of choice in the fabrication of nanoparticles for use in imaging diagnostics, medical therapeutics, and tissue engineering because of its biocompatible nature. However, recent evidence suggests that silica nanoparticles (SiNPs) show a concentration- and size-dependent toxic effect that is cell specific. We investigated the direct influence of SiNP uptake on the vasodilator responses of rat aortic vessels, in vitro, using fabricated SiNPs of defined size (97 ± 7.60 and 197 ± 7.50 nm) and charge (positive and nonmodified). Dilator responses to cumulative doses of endothelial-dependent [acetylcholine (Ach); 0.01 µM-1.0 mM] and endothelial-independent (sodium nitroprusside; 0.01-10 µM) agonists were determined before and 30 Min after incubation in SiNPs (at 1.1 × 10(11) nanoparticles/mL). Acute exposure to SiNPs led to their rapid uptake by the lining endothelial cells (as verified by transmission electron microscopy). SiNP uptake had no significant influence on dilator responses, although a greater degree of attenuation was evident after uptake of the 100 nm and positively charged SiNPs (significant at the highest 1.0 mM Ach concentration between positive and nonmodified 200 nm SiNPs; P < 0.05). In summary, our findings suggest that SiNP surface interactions, rather than mass, affect vasodilator function of aortic vessels.