声/磁多功能造影剂微泡的包膜特性、动力学响应及生物效应研究

Development of micro/nanometer scale particles that can integrate multiple diagnostic and therapeutic functions is a key focus in both biomedical engineering and nanotechnology, which will have far-reaching impact on medical diagnosis and therapies. However, constructing safe and efficient multifunctional agents has been recognized to be rather challenging. In this project, a new type of multifunctional magnetic microbubble agent would be constructed by coupling superparamagnetic iron oxide nanoparticles (SPIOs) and/or anti-cancer paclitaxel (PTX) to perfluorocarbon-filled microbubbles encapsulated with albumin shell, which can be used for both multimodal imaging contrast agents and in-situ gene/drug delivery carriers. Moreover, it is commonly accepted that the dynamic responses of MBs would be strongly dependent on the structural properties of their encapsulation shells. Thus, in order to get in depth understanding on how the characteristics and functionalities of magnetic microbubble would be affected by the embedding of magnetic nanoparticles, various microbubble physical characteristics (e.g., size distribution, shell stiffness, acoustic scattering and magnetic response), as well as the thermal and biological effects associated with ultrasound-induced microbubble cavitation activities, were systemically examined under different SPIO concentrations. The construction and design of this new type multifunctional imaging and therapeutic agent might open new possibilities to develop more ideal non-invasive controllable diagnostic and treatment strategies that can simultaneously provide accurate imaging information and efficient therapies for earlier cancer diagnosis and treatment, gene/drug delivery, blood-brain barrier opening, etc.

目前，恶性肿瘤已经成为我国大中城市居民第一位死亡原因。而研究显示，毫米级以下的早初期癌症病人有80%-90%以上的治愈可能。因此，早初期癌症的精确诊疗已经成为生命科学、临床医学等诸多领域的关注热点。本课题拟将磁性纳米颗粒、包膜造影剂微泡和抗癌药物相结合，构建一种在高精度多模态影像诊断同时可实现高效无创癌症治疗的新型声/磁多功能造影剂微泡；同时，基于多种实验测量系统，在不同参数条件下，对微泡的包膜特性、声学和磁学特性等进行定征，系统研究磁性纳米颗粒及包膜成分变化对微泡包膜结构特性及其动力学响应的影响；并通过研究超声作用下声/磁造影剂微泡声空化行为引发的热效应和生物效应的参数相关性，深入研究其促进靶区组织热消融或药物输运的作用机制，为早初期肿瘤精确、安全、高效诊疗供关键的理论基础、策略支持和关键技术保障，最终达到控制和优化其临床诊疗效果的目的。

目前，恶性肿瘤已经成为我国大中城市居民第一位死亡原因。而研究显示，毫米级以下的早初期癌症病人有80%-90%以上的治愈可能。因此，早初期癌症的精确诊疗已经成为生命科学、临床医学等诸多领域的关注热点。本课题拟将磁性纳米颗粒、包膜造影剂微泡和抗癌药物相结合，构建一种在高精度多模态影像诊断同时可实现高效无创癌症治疗的新型声/磁多功能造影剂微泡；同时，基于多种实验测量系统，在不同参数条件下，对微泡的包膜特性、声学和磁学特性等进行定征，系统研究磁性纳米颗粒及包膜成分变化对微泡包膜结构特性及其动力学响应的影响；并通过研究超声作用下声/磁造影剂微泡声空化行为引发的热效应和生物效应的参数相关性，深入研究其促进靶区组织热消融或药物输运的作用机制，为早初期肿瘤精确、安全、高效诊疗供关键的理论基础、策略支持和关键技术保障，最终达到控制和优化其临床诊疗效果的目的。

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