Targeted CT imaging of human hepatocellular carcinoma using low-generation dendrimer-entrapped gold nanoparticles modified with lactobionic acid

Abstract

Development of cost-effective nanoscale contrast agents for targeted tumor computed tomography (CT) imaging remains a great challenge. Here, we report the synthesis of dendrimer-entrapped AuNPs (Au DENPs) using generation 2 poly(amidoamine) dendrimers pre-modified with fluorescein isothiocyanate via a thiourea linkage and lactobionic acid (LA) via a polyethylene glycol spacer as templates. The formed Au DENPs were characterized via different techniques and were used as a nanoprobe for targeted CT imaging of hepatocellular carcinoma (HCC). We show that the LA-modified Au DENPs with a mean Au core size of 1.8 nm are water-dispersible, colloidally stable under different temperatures (4–50 °C) and pH (5–8) conditions, and cytocompatible in the studied concentration range. Flow cytometry results reveal that the LA-Au DENPs are able to specifically target HepG2 cells (a human HCC cell line) overexpressing asialoglycoprotein receptors via a receptor-mediated targeting pathway. Importantly, the developed LA-Au DENPs can be used as a nanoprobe for targeted CT imaging of HepG2 cells in vitro and the xenografted tumor model in vivo. With the demonstrated organ compatibility, the developed LA-Au DENPs using low-generation dendrimers as templates can be a good candidate to be used as a highly efficient and cost-effective nanoprobe for targeted CT imaging of HCC.