新型超声造影剂的力学特性与模型研究

Newtype ultrasound contrast agents are gas-filled microcapsules with specific ligand attached to the shell surface and drugs or gene loaded in the shell or core. They have great potential as carriers for drug delivery, gene therapy, thrombolysis, tumor target imaging and therapy. In order to design newtype ultrasound contrast agents, it is crucial to understand the mechanical properties of the shell material and the mechanical behavior of the microcapsules when they are exposed in ultrasound radiation. The traditional model based on Rayleigh-Plesset eqatuions for microbubbles and microcapsules is not applicable for the newtype ultrasound contrast agents. Therefore in this project, according to the microstructural peculiarity of the microcapsule shell, we intend to study the constitutive relation of the shell material and the influence of physiological environment (temperature, pH) on the mechanical properties of the microcapsule shell, by means of molecular dynamic simulation and microforce experiment. Then we establish the mechanical model for the microcapsules and further solve the mechanical response to the external load, using the existing theoretical system and solving methodology from continuum mechanics. Meanwhile, we conduct corresponging mechanical experiments for model improvement and validation. The performance of mechanical response of newtype ultrasound contrast agents under ultrasound excitation determines the effect of ultrasound imaging and therapy. This research will provide a theoretical model and computing approach for newtype ultrasound contrast agents in mechanical characteristic design and clinic applications.

新型超声造影剂是内含气体的微囊，表面修饰特异性配体，壳体或壳内携带药物或基因，可应用于药物输送、基因治疗、溶栓治疗、肿瘤靶向显影与治疗等方面。在新型超声造影剂的设计过程中，需要对微囊壳体材料的力学性质以及微囊在超声辐射作用下的力学行为进行分析，以Rayleigh-Plesset方程为基础的传统微泡微囊模型不再适用于新型造影剂。本项目计划从微囊外壳的微观结构特点着手，利用分子动力学模拟和微力加载实验等手段，分析壳材料的本构关系以及生理环境（温度，pH值）对微囊外壳力学性质的影响，然后利用现有的连续介质力学的理论框架和求解体系，建立微囊的力学模型并求解其在外部载荷作用下的力学响应，同时进行相应的力学实验进行验证。新型造影剂在超声激励下的力学响应性能决定了超声显影与治疗的效果，本项目的研究将为新型超声造影剂的力学性能设计与临床应用研究提供理论模型与计算方法。

新型超声造影剂是内含气体的微囊，表面修饰特异性配体，壳体或壳内携带药物或基因，可应用于药物输送、基因治疗、溶栓治疗、肿瘤靶向显影与治疗等方面。在新型超声造影剂的设计过程中，需要对微囊壳体材料的力学性质以及微囊在超声辐射作用下的力学行为进行分析，以Rayleigh–Plesset方程为基础的传统微泡微囊模型不再适用于新型造影剂。本项目从微囊外壳的微观结构特点着手，利用分子动力学模拟和微力加载实验等手段，分析壳材料的本构关系以及生理环境（温度，pH值等）对微囊外壳力学性质的影响，然后利用现有的连续介质力学的理论框架和求解体系，建立微囊的力学模型并求解其在外部载荷作用下的力学响应，同时进行相应的力学实验进行验证。相关研究结果表明，微观尺度下材料的模拟结果经过非局域化处理，与大尺度下材料的力学实验结果对比具有可比性。通过高分子材料的薄膜压陷实验和微囊压缩实验，能够计算出微囊壳体材料力学的参数。因此，有可能在今后载药微囊的设计过程中，通过数值模拟研究这种相对快速、低成本的手段，为微囊设计初期的大规模方案筛选提供参考。大幅度降低载药微囊外壳新材料的试制与性能实验需所要负担的时间和经费消耗。