Dendrimer-Stabilized Bi₂S₃ Nanoparticles: Synthesis, Characterization And Their Application In CT Imaging

Nanoparticles (NPs) continue to receive immense attention as a result of their peculiar and fascinating properties in optoelectronics, catalysis, and biomedicine. In particular, there has been increasing importance in the use of NPs as imaging probes for in vivo biomedical applications. X-ray computed tomography (CT) as one of the most common medical imaging tools for evaluating nearly all organ systems with high spatial and density resolution is used frequently in hospital. Clinical CT contrast agents (e.g., Omnipaque), which are based on iodine-containing small molecules, have several drawbacks, such as short circulation times, renal toxicity, and non-specificity, limiting their applications. Hence, effort has been extensively made to search other metal elements to substitute iodine. Bi with a higher atomic number than iodine is expected to have a higher X-ray absorption coefficient than iodine, and could theoretically cause greater contrast enhancement in CT imaging. Therefore, Bi2S3 NPs have a great potential to be used as a promising contrast agent in CT imaging applications.In this work, we attempted to use ethylenediamine core poly(amidoamine) (PAMAM) dendrimers of generation 4 terminated with hydroxyl groups (G4.NGlyOH) as stabilizers to synthesize dendrimer-stabilized Bi2S3 NPs (Bi2S3 DSNPs). The formed Bi2S3 DSNPs were characterized by UV-Vis spectrometry, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS). The results indicate that Bi2S3 DSNPs have been successfully synthesized. By varying the molar ratio of bismuth salt to dendrimer, a series of Bi2S3 DSNPs with a size range of 7-9 nm can be prepared.The biocompatibility of Bi2S3 DSNPs was investigated by analyzing their cytotoxicity and hemolytic effects. MTT assay and hemolysis assay indicate that the Bi2S3 DSNPs are biocompatible at the studied concentration range. In addition, the X-ray attenuation property of the prepared Bi2S3 DSNPs was investigated by X-ray absorption coefficient measurements. The X-ray attenuation of Bi2S3 DSNPs was found to be much higher than that of Omnipaque at the same molar concentration of the active element (bismuth versus iodine). The Bi2S3 DSNPs were also used for in vitro CT imaging of KB cells. Micro-CT images show that KB cells can be detected under X-ray after incubation with the Bi2S3 DSNPs in vitro. Finally, the CT imaging capability was tested by injecting subcutaneously into a rabbit with Bi2S3 DSNPs. The experiment result displays that the subcutaneously injected Bi2S3 DSNPs can significantly increase the contrast of the injection region of a rabbit in the CT image. All results of this research suggest that the biocompatible Bi2S3 DSNPs may be used as a highly efficient CT imaging contrast agent for medical molecular imaging applications.