pHIFU介导载药声敏脂质体增强药物靶向释放应用机制实验研究

项目名称： pHIFU介导载药声敏脂质体增强药物靶向释放应用机制实验研究

项目编号： No.81471664

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 朱江

作者单位： 浙江大学

项目金额： 70万元

中文摘要： 由于高强度聚焦超声（HIFU）介导的载药微泡靶向治疗一般是利用超声波的热效应和空化效应，具有温度不易控制及易对周围正常组织造成损伤等缺点，本研究将完善具有专属性热效应和振动效应的脉冲式高强度聚焦超声（pHIFU）设备的软硬件，并构建一种新型声敏脂质体给药系统，通过调整DPPC与HSPC的配比，使其相变温度与pHIFU介导的热传递相匹配，通过控制pHIFU系统的工作状态，建立基于超声共振治疗的物理模型,使其能在药物靶向投送区域与脂质体作用并产生非线性共振效应，由此达到化疗药物能定点定量和安全有效投送的目的，并通过比较不同超声波强度所引发的热效应、空化效应和共振效应，分析应用可控的非线性共振效应在提高化疗药物在肿瘤部位的局部浓度，有效杀伤肿瘤组织和减少对正常细胞的伤害的效果，并通过实验揭示超声波介导靶向治疗的相关机制。

中文关键词： pHIFU；靶向治疗；脂质体；化疗

英文摘要： Drug loaded microbubbles targeted therapy mediated by high intensity focused ultrasound (HIFU) normally achieved by using thermal and cavitation effects, which had shortcomings such as non-temperature control and likely to cause damage to the surrounding normal tissues，etc. Our study designed a novel drug delivery system, called ultrasound sensitive liposomes. Through adjusting the ratio of DPPC and HSPC, the phase-transition temperature of liposomes matched the thermal transmission mediated by pHIFU. By controlling the working state of pHIFU system, beginning with interaction between ultrasonic and drug loaded ultrasound sensitive liposomes, according to the theories and experimental data of acoustics, material science and biomedicine, establishing the physical model based on ultrasonic resonance therapy, and revealing the action mechanism and law of ultrasonic by means of experiments, so that the drugs can be delivered to targeted spatiality and interacted with liposomes which resulted in the non-linear resonance effect. Thus，the goals that delivering chemotherapeutic drugs quantitatively, spatially, safely and effectively are accomplished.The project achieved accurate control of ultrasound sensitive liposomes'vibrational state in living tissues by regulating the intensity of ultrasonic. By comparing the thermal, cavitation and resonance effects initiatd by different ultrasonic intensities, and analyzing the rusults of non-linear resonance effect on enhancing the local concentration of chemotherapeutic drugs in tumor sites, effective killing of tumor tissues, reducing the damage to normal cells and systemic adverse reactions. Further study on related mechanisms of targeting therapy mediated by ultrasound.

英文关键词： pHIFU;target therapy;liposomes;chemotherapy