Efficacy enhancement of folate-receptor targeted phasetransition contrast agent for HIFU ablation of tumor in vivo / 中华超声影像学杂志

ABSTRACT

Objective To explore the value of Folate-receptor targeted phaseransition nanoparticle contrast agent (FR PNPCA) in increasing efficacy of high intensity focused ultrasound (HIFU) ablation of xerograft tumor in vivo.Methods Firstly,the FR-PNPCA and non targeted phasetransition nanoparticle contrast agent (PNPCA) were prepared by a two step emulsification method respectively.Then 36 nude mice bearing xerograft ovary tumor were randomly divided into 3 groups and underwent HIFU ablation respectively.Group A was the control group,which was irradiated at 2 h after the injection of saline by the tail vein.Group B was the untargeted group,which was irradiated at 2 h after the injection of PNPCA.Group C was the targeted group,which was irradiated at 2 h after the injection of FR-PNPCA.The gray scale changes of irradiating areas in tumors were observed during ablation.Some mice were sacrificed at 1 h after ablation and the tumors were resected to observe the coagulative necrosis by TTC staining and HE staining.Lastly,The remain mice were sacrificed at 24 h after ablation,and the tumor sections were analyzed with immunohistochemical method including PCNA and TUNEL to explore the effect of HIFU ablation on tumor cell proliferating and necrosis.Results Obvious gray-scale changes could be seen in all tumors in group B and C immediately after HIFU irradiation,but almost no changes were founded in group A.The differences of gray-scale change values and squares between group B and C were statistically significant (P ＜0.05).Coagulative necrosis with irregular shape and clear boundary was observed in group B and C after irradiation,and the range of necrosis in group C was much larger than that in group B (P ＜ 0.01),but little necrosis was founded in group A.In addition,the differences of proliferating rate and necrosis rate between group B and C were statistically significant (P ＜0.05).Conclusions FR-PNPCA can not only significantly enhance the efficacy,but also can help monitoring the process during HIFU ablation of tumor ablation.Therefore,it is a promising synergistic agent for HIFU ablation.