Targeted Theranostic Nanoprobes for US/MRI Dual-mode Imaging and High Intensity Focused Ultrasound Synergistic Therapy:An in Vitro Experiment / 中国医学影像学杂志

ABSTRACT

Purpose To develop the folate-targeted theranostic nanoprobe, investigate the active targeting behavior of nanoprobes to hepatocellular carcinoma(HCC)in vitro,and discuss the effect of enhanced US/MRI dual-mode imaging in vitro and the synergistic effect of high intensity focused ultrasound on HCC killing. Materials and Methods The folate-targeted nanoprobe loaded with iron oxide nanoparticles (Fe3O4) and phase-shift material perfluorohexane (PFH) was prepared by double emulsion method and carbodiimide method. The average particle size, morphological structure and the ability of liquid-gas phase transition were detected. The active targeting ability of the nanoprobe to HCC BEL-7402 was observed in vitro.The ultrasonic imaging effect of nanoprobe was observed by HIFU irradiation in vitro.MRI was performed on the Fe3O4nanoprobe with different content of magnetic particles.The synergistic killing ability of the nanoprobe combined with HIFU on liver cancer cells was detected with in vitro apoptosis experiment. Results The folate-targeted nanoprobe loading iron oxide nanoparticles (Fe3O4) and phase-shift material PFH was prepared, with the average size of (402.50±66.43) nm. It was in the shape of regular sphere with the magnetic particle Fe3O4scattered inside. The HIFU irradiation caused liquid and gas phase transition.In vitro targeting experiments showed that BEL-7402 cells were surrounded by a large number of nanoscale probes.In vitro dual mode imaging showed that the ultrasonic echo intensity was obviously enhanced after HIFU irradiates nanoscale probes. The MR negative imaging ability of the nanoprobe was also enhanced with the enhancement of Fe3O4concentration in nanoparticles. In vitro apoptosis experiments showed that the nanoscale probe had the ability to significantly enhance the effect of HIFU on the killing of HCC. Conclusion The prepared folate-targeted theranostic nanoprobes exhibit the excellent capability for in vitro targeting.They can be used for ultrasound and MRI as multimodal imaging agents and coordinates with HIFU to enhance the effect on killing HCC, which realizes the early diagnosis of tumor and targeted precision therapy.