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

摘要

Objectives In this study, a novel targeted MRI contrast agent was developed by coating gadolinium oxide nanoparticles ( Gd_2O_3 NPs) with β-cyclodextrin (CD)-based polyester and targeted by folic acid (FA). Materials and methods The developed Gd_2O_3@ 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. Results In vitro cytotoxicity and hemolysis assays revealed that Gd_2O_3@ PCD-FA NPs have no significant cytotoxicity after 24 and 48 h against normal human breast cell line (MCF-10A) at concentration of up to 50 μg Gd+ 3/mL and have high blood compatibility at concentration of up to 500 μg Gd+ 3/mL. In vitro MR imaging experiments showed that Gd_2O_3@ PCD-FA NPs enable targeted contrast T_1- and T_2- 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 Gd_2O_3@ PCD-FA up to 5.89 ± 1.3 within 1 h under T_1- weighted imaging mode and reduced to 1.45 ± 0.44 after 12 h. While CNR increased up to maximum value of 1.98 ± 0.28 after injection of Gd_2O_3@ PCD within 6 h and reduced to 1.12 ± 0.13 within 12 h. Conclusion The results indicate the potential of Gd_2O_3@ PCD-FA to serve as a novel targeted nano-contrast agent in MRI.