为了促进作为肿瘤诊疗剂的相变纳米液滴透过肿瘤内皮血管间隙，并在肿瘤内被有效激发相变以实现对肿瘤的高效诊疗，本申请项目的主要研究内容为：(1)设计和制备一种携载超顺磁性氧化铁颗粒、可利用超声/磁场协同操控的具有双峰粒径分布的双模相变纳米液滴；(2)一种对肿瘤部位的双模相变纳米液滴进行超声/磁场协同操控的方法，该方法主要分为两步：(a)第一步是外加磁场引导+超声空化增强外渗，即首先利用磁力引导使双峰分布的液滴均产生定向移动靠近血管壁，然后再施加较低强度的聚焦超声仅使其中粒径较大的液滴发生相变，相变后导致的空化效应可进一步促进扩大血管内皮间隙，从而促进未相变的小粒径液滴进一步在磁力引导下透过血管壁外渗到肿瘤组织内；(b)第二步是利用交变磁场加热+聚焦超声协同作用使已渗出到肿瘤组织中的双模相变液滴发生相变，从而真正实现肿瘤内的成像及图像引导下的释药和治疗等。

In order to improve the extravasation of cancer theranostic agents – phase-shifted nanodroplets from tumor endothelial gap due to EPR effect, and then get highly effective theranostics by activating the extravasated droplets to vaporize into bubbles within the tumor bed, the aim of this project is focused on studying: (1)design and preparation of double-peak distributed SPIO-loaded bimodal phase-shifted nanodroplets, that can be synergistically manipulated by external focused ultrasound and magnetic field; (2)a two-step ultrasound/magnetic manipulation method for the bimodal phase-shifted nanodroplets: (a)firstly, using magnetic force manipulation + ultrasound cavitation to enhance the extravasation of nanodroplets, i.e., the nanodroplets are forced to move close to the vessel wall by magnetic force, then apply focused ultrasound with lower intensity to acoustically vaporize only the nanodroplets with larger size to microbubbles, the cavitation effect that is accomplished with this process can further increase the endothelial gap, thereby, the smaller nanodroplets can penetrate the vessel wall guided by magnetic force and retain within tumor tissue; (b)secondly, using alternating magnetic field to heat the nanodroplets retained in tumor bed and then using focused ultrasound to activate the nanodroplets phase transform to microbubbles for further application of tumor imaging or therapy.