携HE4的纳米相变卵巢癌造影剂在体内成像实验研究

In vivo imaging of nano phase change ovarian cancer contrast agent carrying HE4#

目的:制备携人附睾蛋白4(Human epididymis protein 4,HE4)的纳米相变卵巢癌造影剂,并联合高强度聚焦超声(High intensity focused ultrasound,HIFU)进行体内靶向超声成像。方法:将聚乳酸-羟基乙酸共聚物(Poly-lactic-co-glycolic acid-cooh),(PLGA-COOH)、全氟已烷(Perfluorohexan,PFH)、人附睾蛋白4-聚乙二醇-氨基(HE4-poly(Ethylene glycol)PEG-NH2)等通过单乳化法及碳二亚胺法进行分散、溶解、离心、冷冻干燥得到人附睾蛋白4-全氟已烷-聚乳酸(HE4-PFH-PLGA)纳米高分子造影剂;实验组将HE4-PFH-PLGA注入裸鼠卵巢癌移植瘤身上通过HIFU辐照。对照组全氟已烷-聚乳酸(PFH-PLGA)造影剂注入裸鼠癌移植瘤通过HIFU辐照及HE4-PFH-PLGA注入裸鼠移植瘤未通过HIFU辐照。结果:HE4-PFH-PLGA在HIFU辐照能发生明显相变,体内超声下有良好的增强显像。对照组没有增强显像。结论:具有液相变的纳米粒HE4-PFH-PLGA是一种新型的卵巢癌靶向超声造影剂。

Objective:To prepare nano phase change ovarian cancer contrast agent carrying human epididymis protein 4(HE4)and conduct targeted ultrasound imaging in vivo in combination with high intensity focused ultrasound(HIFU).Methods:Human epididymal protein 4-perfluorohexane-polylactic acid(he4-pfh-plga)was obtained by dispersing,dissolving,centrifuging and freeze-drying poly lactic acid(plga-cooh),perfluorohexan(PFH)and human epididymal protein 4-polyethylene glycol-amino(HE4 poly(ethylene glycol)PEG-NH2)by single emulsion method and carbodiimide method Nano polymer contrast agent;In the experimental group,he4-pfh-plga was injected into ovarian cancer xenografts in nude mice and irradiated by HIFU.In the control group,perfluorohexane polylactic acid(pfh-plga)contrast medium was injected into nude mice,and the transplanted tumor was irradiated by HIFU and he4-pfh-plga,but not irradiated by HIFU.Results:he4-pfh-plga could significantly change phase under HIFU irradiation,and had good enhanced imaging under in vivo ultrasound.There was no enhanced imaging in the observation group.Conclusion:he4-pfh-plga nanoparticles with liquid phase transition are a new type of targeted ultrasound contrast agent for ovarian cancer.