Superparamagnetic PLGA–iron oxide microspheres as contrast agents for dual-imaging and the enhancement of the effects of high-intensity focused ultrasound ablation on liver tissue

Abstract

Efforts have been made to develop a multifunctional platform that could provide both diagnostic information and a therapeutic effect. In this study, superparamagnetic poly(lactic-co-glycolic acid) (PLGA)–iron oxide (uSPIO/PLGA) microspheres were prepared for application in ultrasound (US) and magnetic resonance imaging (MRI) and the enhancement of the therapeutic efficiency of high-intensity focused ultrasound (HIFU) on liver tissue through an intravenous injection. Highly dispersed, regular spherical and negatively charged uSPIO/PLGA microspheres were fabricated by a typical double emulsion method in which uSPIO nanoparticles were observed and integrated into PLGA microspheres. The Fe (iron) concentration was determined using atomic absorption spectrometry. In our experiment, the uSPIO/PLGA microspheres showed higher echogenicity than PLGA microspheres and saline in US imaging. Furthermore, the uSPIO/PLGA microspheres appeared to negatively enhance T2-weighted (T2WI) magnetic resonance imaging, with the MR signal intensity decreasing with the increase of the Fe content. The uSPIO/PLGA microspheres were introduced into bovine liver and into rabbits to evaluate the HIFU synergistic ablation efficiency in vitro and in vivo. After the intravascular administration of the uSPIO/PLGA microspheres, the liver tissue was ablated by HIFU, and the tissue exposed to HIFU was subjected to pathological examination to determine its structural variation. Pure PLGA microspheres (without uSPIO) and saline were used as the controls. Our results show that the coagulative necrosis volume and degree of liver tissue in the uSPIO/PLGA group was significantly greater than in the PLGA group and saline group. The employment of the composite uSPIO/PLGA microspheres could significantly enhance dual-modality US/MR imaging and HIFU synergistic therapy with an intravenous administration method.