基于靶向氧气纳米传感器的高分辨荧光成像对组织缺氧下肿瘤光动力疗法优化的研究

项目名称： 基于靶向氧气纳米传感器的高分辨荧光成像对组织缺氧下肿瘤光动力疗法优化的研究

项目编号： No.61575017

项目类型： 面上项目

立项/批准年度： 2016

项目学科： 无线电电子学、电信技术

项目作者： 彭洪尚

作者单位： 北京交通大学

项目金额： 16万元

中文摘要： 肿瘤的光动力治疗（PDT）需要分子氧参与，但肿瘤组织中溶氧量过低（组织缺氧）限制氧的供给而削弱了PDT疗效。并且，随着氧的消耗，PDT会加剧组织的缺氧水平，增强癌细胞的增殖能力和耐药性。因此，实时了解PDT作用下肿瘤微环境中溶氧分布对于提高治疗效果具有重要意义。目前对组织缺氧的荧光成像已经开展了很多工作，但大都局限于整体成像（分辨率低）以检测肿瘤，对PDT作用下肿瘤微环境内溶氧的高分辨成像则鲜有报道。本项目拟利用肿瘤多细胞球模拟实体肿瘤，利用靶向线粒体的纳米传感器探测细胞内溶氧变化最剧烈的区域，使用激光共聚焦显微镜对PDT作用下肿瘤微环境的溶氧进行高分辨荧光成像。并在PDT过程中基于探测到的溶氧量及时调整治疗参数，并通过单层细胞系、肿瘤多细胞球和活体肿瘤依次优化筛选。该项目的开展有望得到肿瘤多细胞球内溶氧分布的高分辨荧光成像，建立起溶氧扩散和消耗的理论模型，并获取优化的肿瘤PDT治疗参数。

中文关键词： 光动力治疗；组织乏氧；荧光；氧气传感；肿瘤

英文摘要： Molecular oxygen is indispensible to the efficacy of photodynamic therapy (PDT), while tumor hypoxia restricts the supply of oxygen. Moreover, PDT can further decrease the concentration of oxygen and increase the proliferation and resistant of tumor cells. Therefore, the PDT efficacy can be greatly improved if the concentration of dissolved oxygen, during the process of PDT treatment, within tumor microenvironment is monitored with high spatial and temporal resolution. Although many studies have been reported to image hypoxia, most of them are just whole-body imaging with the aim to detect tumor. Up to now, oxygen concentration in tumor microenvironments under PDT treatment has rarely been studied. In this proposal, (multicellular tumor spheroids, MCTs) are adopted to simulate solid tumors, and mitochondrial targeted oxygen nanosensors are used to image the intracellular area with severely varied oxygen based on the high-resolved confocal microscope. All those make it is possible to image the dissolved oxygen within tumor microenvironments with high resolution. At the same time, the PDT parameters will be timely adjusted according to the concentration of oxygen, which are optimized through monolayer tumor cells, MCTs and in vivo tumor in sequence. With the performance of this proposal, high-resolved imaging of d

英文关键词： photodynamic therapy；tissue hypoxia；fluorescence；oxygen sensing；tumor