Use of the Highly Biocompatible Au Nanocages@PEG Nanoparticles as a New Contrast Agent for In Vivo Computed Tomography Scan Imaging

Abstract

In recent years, contrast agents have been widely used in imaging technology to improve quality. Nanoparticles have better in vivo detection capability than conventional molecular scale contrast agents. In this study, a new type of Au nanocages@PEG nanoparticles (AuNC@PEGs) with a strong X-ray absorption coefficient was synthesized as a contrast agent for computed tomography (CT) scan imaging. Results showed that AuNC@PEGs had good aqueous dispensation, low cytotoxicity, and strong X-ray absorption ability. Furthermore, in vivo studies have shown that the synthesized AuNC@PEGs have an evident contrast enhancement, long circulation time in the blood, and negligible toxicity in vivo. Therefore, the synthesized functionalized AuNC@PEGs in this study have great potential for clinical application in CT scan imaging.

Keywords: AuNC@PEGs; Biocompatibility; Contrast agent; In vivo CT imaging.

Fig. 1

TEM images of AuNC@PEGs (a) and DLS of AuNC@PEGs (b)

Fig. 2

MTT evaluation of the viability of HUVEC cells cultured with different AuNC@PEGs concentrations for 24 h (a). Assessment of lactate dehydrogenase in supernatant induced by AuNC@PEGs with LDH (b). Examination of 24 h fluorescence imaging of cells cultured with AuNC@PEGs at different concentrations (H₂O₂ (I), 0 μg/mL (II), 50 μg/mL (III), 100 μg/mL (IV), 200 μg/mL (V) and 500 μg/mL (VI)) by ROS method (c). *P < 0.05, ***P < 0.001. Scale bars are 100 μm

Fig. 3

Fluorescence microscopy images of live and dead staining. Survival rate of HUVEC cells treated with AuNC@PEGs at different concentrations (0 μg/mL (a), 10 μg/mL (b), 20 μg/mL (c), 50 μg/mL (d), 100 μg/mL (e), 200 μg/mL (f), 500 μg/mL (g), and 1000 μg/mL (h)) for 24 h. Green fluorescence represents living cells and red fluorescence represents dead cells. The scale bars are 100 μm

Fig. 4

Comparison of computed tomography scan findings in vitro between AuNC@PEGs and iodine-based contrast agent. As the concentration increases, the intensity of X-ray attenuation increases (a). Comparison of Hu values between AuNC@PEGs and iodine-based contrast agents (b). ***P < 0.001

Fig. 5

In vivo CT images of the rats at different time points after post-injection of AuNC@PEGs

Fig. 6

In vivo toxicity evaluation of AuNC@PEGs. Blood routine and liver and kidney function: hemoglobin level (I), mean corpuscular hemoglobin concentration (II), mean corpuscular volume (III), platelet (IV), red blood cell count (V), white blood cell count (VI), albumin concentration (VII), alanine aminotransferase level (VIII), aspartate aminotransferase level (IX), and creatinine level (X) (a). H&E staining was performed in the organs (the heart, liver, spleen, lung, and kidney) of normal rats and those injected with AuNC@PEGs for 24 h (b). The scale bars of b are 100 μm