多功能载药磁性纳米探针构建及其评价EPCs治疗心肌梗死的多模态影像研究

Cardiovascular diseases are emerging as the gravest threats to human beings; especially myocardial infarctions are particularly common. The previous studies demonstrated that vascular endothelial growth factor (VEGF) transfected endothelial progenitor cells (EPCs) transplantation are potential to improve cardiac function and clinical prognosis, and this method will achieve a good clinical prospects. However, the mechanism of combination the VEGF with EPCs are collaboratively beneficial to treatment need be further validated, and the molecular methods of the therapeutic procedure trace and treatment effects assessment are necessary. In this proposal, we intend to innovatively synthesis nanoprobe (PEI-C12/SPIO/plasmid) with VEGF and Luc, and to achieve the multifunction nanoprobe including gene drug carrier and bimodal molecular imaging (MRI and bioluminescence imaging). The biological safety of the probe will be verified by MTT assay, cell autophagy and myocardial toxicity test. Moreover, our study will dynamically trace the distribution and survival status of EPCs labeled with nanoprobe using bimodal molecular imaging. Combined with perfusion and functional MR imaging, we are hopeful that the therapeutic process would be dynamically monitored and the treat effects could also be noninvasively assessed in vivo with multimodal molecular imaging. Furthermore, the synergistic effects of VEGF transfected EPCs will be validated and the synergistic mechanism of angiogenesis and regeneration will be further clarified in our study. Most importantly, the research proposal may be potential to establish new strategies and methods for monitoring dynamically the therapeutic procedure and assessing noninvasively the treatment effects in clinical practice.

心血管疾病已逐渐成为社会危害最大的疾病，其中心肌梗死尤为常见。研究表明血管内皮细胞生长因子（VEGF）转染内皮祖细胞（EPCs）协同移植治疗心肌梗死可以提高心脏功能和改善患者预后，有较好的临床应用前景。但是，目前VEGF转染EPCs移植后的协同作用机制尚待进一步阐释，需要基于分子水平的治疗监测和疗效评价方法。有鉴于此，本课题组拟创新性构建兼具分子成像和基因载药能力的多功能复合纳米分子探针（PEI-C12/SPIO/plasmid），并通过MTT法、细胞自噬及心肌毒性评价等方法充分验证其生物安全性。通过探针携带VEGF和Luc报告基因，同时实现协同治疗和双模态分子成像（生物发光和MRI），进行无创、活体、动态监测移植后EPCs细胞的分布和存活情况；结合心脏功能、灌注及延迟成像等方法，实现动态监测治疗过程和量化评价治疗效果，并进一步探索相应的协同作用机制，为治疗决策和疗效评价提供新思路和新方法

前期研究表明血管内皮细胞生长因子（VEGF）转染内皮祖细胞（EPCs）协同移植治疗心肌梗死可以提高心脏功能和改善患者预后，有较好的临床应用前景。但是，目前VEGF转染EPCs移植后的协同作用机制尚待进一步阐释，需要基于分子水平的治疗监测和疗效评价方法。有鉴于此，本课题组拟创新性构建兼具分子成像和基因载药能力的多功能复合纳米分子探针（PEI-C12/SPIO/plasmid），并通过 MTT法、细胞自噬及心肌毒性评价等方法充分验证其生物安全性。通过探针携带VEGF和Luc报告基因，同时实现协同治疗和双模态分子成像（生物发光和MRI），进行无创、活体、动态监测移植后EPCs细胞的分布和存活情况；结合心脏功能、灌注及延迟成像等方法，实现动态监测治疗过程和量化评价治疗效果，并进一步探索相应的协同作用机制，为治疗决策和疗效评价提供新思路和新方法。相关研究在国际重要学术刊物Journal of Biomedical Nanotechnology，2019（IF：5.068）发表SCI论文1篇，中文期刊文章2篇，另有相关文章正在准备投稿并申请专利。申请者带领团队晋升副教授3名，培养博士研究生3名；申请人获评“四川省学术技术带头人后备人才”。