Objective To prepare a nanoscale ultrasound molecular probe carrying liver cancer therapeutic gene plasmid and folic acid（FA） targeting

and to study its basic characteristics and ultrasound imaging ability.Methods Pegylated imine was used to connect FA molecules on the surface of PLGA to prepare targeted membrane material（PLGA-FA）

then PFPloaded nanoscale targeted ultrasound contrast agent was prepared by double emulsification method

and positively charged cations were formed on the surface after incubation with polylysine

and S-HSV1-TK were loaded on the surface of nanoparticles by positive and negative charge adsorption

then S-HSV1-TK/PFP@FA-PLGA was obtained.The nanoparticles were treated by low intensity focased ultrasound（LIFU） irradiation.The phase change was observed under a microscope

and the image effect in vitro was observed under contrast-enhanced ultrasound mode.The connection rate was detected by flow cytometry.The nontarge ted contrast agent without FA was prepared by PLGA instead of FA-PLGA by the same method.The targeted contrast agent and the non-targeted contrast agent were incubated with HepG2 of liver cancer cells respectively to observe their target-seeking ability in vitro.Results The nanoscale targeted ultrasound contrast agent S-HSV1-TK/PFP@FA-PLGA loaded with plasmid and PFP was successfully prepared.The nanoparticles were uniform in size

good in dispersion

with average particle size of（200.50±66.34） nm and average surface potential of（37.40±7.08） mV.After 5 min of LIFU irradiation

more nanoparticle phase trasitions were observed under the microscope

as well as contrast-enhanced ultrasound.The connection rate of nanoparticle was about 95% by flow cytometry

and the cell experiment results in vitro showed that the targeted contrast agent had an obvious targeting effect.Conclusion A nanoscale targeted ultrasound contrast agent S-HSV1-TK/PFP@FA-PLGA with plasmid and PFP was successfully prepared in this study.The nanoparticles can be used for ultrasound contrast imaging and have tumor targeting

which lays a good foundation for the study of plasmid transfection and tumor treatment.