Engineering and quantification of bismuth nanoparticles as targeted contrast agent for computed tomography imaging in cellular and animal models

Abstract

Bismuth nanoparticles (Bi-NPs) are developed for use as computed tomography (CT) contrast agents (CAs). Herein, the dopamine (DOPA) coated Bi-NPs were synthesized and further functionalized with polyethylene glycol and MUC-16 aptamer (Bi-DOPA-PEG-I-MUC16 NPs). Outside the physicochemical characteristics, in vitro cytotoxicity of Bi-NPs was determined in HeLa and CHO cell lines. The contrast to noise ratio (CNR) effect and figure of merit (FOM) were evaluated at different exposure factors in phantom and cellular tests. Furthermore, the in vivo biodistribution of CAs was investigated by CT imaging and inductively coupled plasma mass spectrometry (ICP-MS) in different organs of rats. The CT number and CNR of Bi-NPs was 8.9 and 13 folds higher, respectively than the commercial CA at equivalent concentrations and similar radiation parameters. With increasing tube current (mA) and tube voltage (kVp), the FOM increased, and conversely, the kVp, CT-values, and CNR was reduced. In vitro results have revealed that the MUC-16 aptamer-targeted Bi-NPs have a 6-fold higher X-ray attenuation ratio than non-targeted Bi-NPs. In vivo results highlighted that synthesized NPs significantly enhance the CT-value and CNR more than iodine-based contrast. These findings have suggested the MUC-16 aptamer targeted NPs as promising targeted CT contrast agents for molecular imaging.