ObjectiveTo investigate the therapeutic effect of high intensity focused ultrasound（HIFU）combinedwith folic acid receptor-targeted 10-hydroxycamptothecin（10-HCPT）-loaded phase-change nanoparticle contrast agent（FR-HCPT-PNPCA）on xenograft hepatoma in nude mice.MethodsOne hundred and twenty tumor-bearing nude mice injectedsubcutaneoushy by human hepatocellular cancer cel（lSMCC-7721）were randomly divided into 4 groups

and 200 μl of drug(orsaline was injected into the tail vein one day before HIFU treatment respectively.Group A was injected by normal saline+HIFUirradiation

irradiation

group B was injected by HCPT+HIFU irradiation

group C was injected by targeted non-drug loadedphase change nanoparticles FR-PNPCA + HIFU irradiation

and group D was injected by targeted drug loaded phase changenanoparticles HCPT-PNPCA + HIFU irradiation. Immediately after irradiation

the grayscale changes in the tumor area were observed by ultrasound.2 h later

10 nude mice were killed in each group.TTC staining of tumors and HE staining of tumorsections were performed to observe coagulation necrosis of tumor cells respectively. The intratumor HCPT concentration wasexamined by tissue homogenate examination.48 h later

10 nude mice were killed in each group again.The tumor sections werestained with PCNA and TUNEL to observe the effect of treatment on tumor cell proliferation and apoptosis respectively.2 weekslater

the remaining nude mice were killed

the size of the tumor was measured

and the main organs were taken out to observe thetumor metastasis.ResultsThere was no change in grayscale in the irradiated areas of groups A and B

and significant grayscalechanges were found in groups C and D.The area and value of grayscale change before and after irradiation of groups C and D werestatistically different from those in groups A and B（all P<0.05）.After 2 h irradiation

HCPT can be detected in tumors of groupsB and D

and the concentration of HCPT in tumors of group D was higher

which was statistically different from that of group B（P<0.05）.Furthermore

no obvious coagulation necrosis was found in groups A and B

while obvious coagulative necrosis wasfound in the tumors of groups C and D

which were statistically different from that of groups A and B（all P<0.01）.The tumor cellproliferation rate was the lowest and apoptosis rate was the highest in group D

the difference compared with A

B

C groups werestatistically significant（all P<0.05）.After irradiation 2 weeks

the tumor in group D almost disappeared

and the metastasis wasthe least

and the difference compared with A

B

C groups were statistically significant（all P<0.05）.ConclusionNot only thetargeted phase-change nanoparticles loading 10-HCPT combined with HIFU treatment can monitor the HIFU ablation of tumorin real time and enhance the HIFU ablation effect

but also can release the loading drug to assist the treatment of the tumor

which is expected to provide a precise and efficient tumor treatment method.