诱导多能干细胞（iPSC）定向分化为NK细胞能有效抑制肿瘤生长，但存在病毒诱导体系安全性欠佳、NK细胞靶向性不足等问题。针对这些问题，基于前期研究基础，特别是在超声联合微泡介导基因转染、多种超声微泡制备、疾病特异性iPSC建系等方面的研究经验，本项目拟对超声联合多功能超声微泡促体细胞重编程及肿瘤靶向免疫治疗进行探索。通过构建基因携载量高的多功能超声微泡，联合超声介导体细胞重编程获得iPSC，并诱导其分化为NK细胞（iPSC-NK细胞），将iPSC-NK细胞与双模态靶向微泡结合，形成NK细胞-微泡复合体，借助声辐射力协同配体提高肿瘤靶向治疗效果，同时采用超声/荧光双模态分子成像技术示踪以评估疗效。本项目旨在通过超声联合微泡这一非病毒方法安全、高效地建立iPSC系，以无创、靶向、可视化的手段为肿瘤的细胞免疫治疗提供一种新策略。

Although induced pluripotent stem cells (iPSCs) can differentiate into NK cells, which can inhibit the growth of tumor efficiently, many obstacles need to be overcome, including safety problems of viral transduction and inefficient homing of NK cells to tumor sites. In order to tackle these problems, we intent to investigate tumor targeting immunotherapy and somatic cell reprogramming with the combination of ultrasound and microbubbles. This program is based on our previous research especially on ultrasound mediated gene transfection, preparation of multiple microbubbles and disease-specific iPSCs generation. In this research, we will prepare a multifunctional microbubble with high gene loading capacity and generate iPSCs from somatic cells with the assistance of ultrasound and microbubbles, obtaining therapeutic NK cells(iPSC-NK cells)from iPSC for tumor immunotherapy. Combining with tumor targeted dual-modal microbubbles and acoustic radiation force, iPSC-NK cells will accumulate selectively in the tumor site. We will also monitor NK cells in vivo and estimate the efficacy with ultrasound and optical molecular imaging. This program aims to produce iPSCs efficiently and provide a novel strategy for non-invasive, visible and targeted tumor immunotherapy with the application of ultrasound and microbubbles.