Folic Acid-targeted Phase Transition PLGA Nanoparticles For Imaging And Therapy Of Hepatocellular Carcinoma In Vivo And In Vitro

Objective: The purpose of this study is to prepare targeted phase transition nanoparticles,so as to achieve contrast-enhanced ultrasound imaging and targeted suicide gene therapy for hepatocellular carcinoma.Methods: Folic acid-targeted,phase transition poly(lactic-co-glycolic acid)(PLGA)nanoparticles loaded with Herpes simplex virus type Ithymidine kinase(HSV1-TK)suicide gene and perfluoropentane(PFP)were prepared by double emulsion method and carbodiimide method.The size distribution,zeta potential and morphological characterization were measured using Malvern measuring instrument and electron microscopy.The targeting performance to the human liver cancer cells SMMC-7721 and Hep G2 were determined by laser scanning confocal microscopy(CLSM).The biocompatibility was evaluated by CCK-8assay,blood analysis and pathological test.A rabbit VX2 orthotopic hepatocellular carcinoma mode and human liver cancer cells SMMC-7721 and Hep G2 were used to evaluate the capability of contrast-enhanced ultrasound imaging and the efficacy of suicide gene therapy in vivo and in vitro.Results: The size of nanoparticles was(207.00 ± 46.06)nm with the shape of regular sphere.In vitro targeting experiments show that targeted nanoparticles aggregated around the human liver cancer cells SMMC-7721 and Hep G2.The nanoparticles with good biocompatibility and with the ability to undergo phase transition by LIFU irradiation to achieve contrast-enhanced ultrasound imaging.Great efficacy of nanoparticles carried HSV1-TK suicide gene to hepatocellular carcinoma was found after using prodrug ganciclovir(GCV).Conclusion: The folic acid-targeted phase transition PLGA nanoparticles with good biocompatibility were successfully prepared and are expected to achieve contrast-enhanced ultrasound imaging and targeted suicide gene therapy for hepatocellular carcinoma.