Gadolinium (III) oxide nanoparticles coated with folic acid-functionalized poly(β-cyclodextrin-co-pentetic acid) as a biocompatible targeted nano-contrast agent for cancer diagnostic: in vitro and in vivo studies.

Abstract

In this study, a novel targeted MRI contrast agent was developed by coating gadolinium oxide nanoparticles (Gd2O3 NPs) with β-cyclodextrin (CD)-based polyester and targeted by folic acid (FA). The developed Gd2O3@PCD-FA MRI contrast agent was characterized and evaluated in relaxivity, in vitro cell targeting, cell toxicity, blood compatibility and in vivo tumor MR contrast enhancement. In vitro cytotoxicity and hemolysis assays revealed that Gd2O3@PCD-FA NPs haveno significant cytotoxicity after 24 and 48h against normal human breast cell line (MCF-10A) at concentration of up to 50µg Gd+3/mL and havehigh blood compatibility at concentration of up to 500µg Gd+3/mL. In vitro MR imaging experiments showed that Gd2O3@PCD-FA NPs enable targeted contrast T1- and T2-weighted MR imaging of M109 as overexpressing folate receptor cells. Besides, the in vivo analysis indicated that the maximum contrast-to-noise ratio (CNR) of tumor in mice increased after injection of Gd2O3@PCD-FA up to 5.89 ± 1.3 within 1h under T1-weighted imaging mode and reduced to 1.45 ± 0.44 after 12h. While CNR increased up to maximum value of 1.98 ± 0.28 after injection of Gd2O3@PCD within 6h and reduced to 1.12 ± 0.13 within 12h. The results indicate the potential of Gd2O3@PCD-FA to serve as a novel targeted nano-contrast agent in MRI.