项目名称： 面向肿瘤诊断和治疗上转换光学一体化探针的构建与应用

项目编号： No.81471726

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 侯毅

作者单位： 中国科学院化学研究所

项目金额： 72万元

中文摘要： 肿瘤的精准定位及有效治疗是肿瘤研究面临的基本问题。基于稀土纳米晶体的上转换光学成像，将光学成像灵敏度高、成像时间短等优点，与上转换发光组织穿透深度大、无自发荧光干扰等优势相结合，可提高肿瘤检测精度。目前广泛研究的Yb3+敏化体系，采用的980 nm激发光与水分子的近红外吸收重叠，长时间照射，可导致照射区域组织温度过高，甚至灼伤。光动力疗法作为肿瘤治疗的新技术，具有创伤小、毒性低、选择性好、安全性高等优点，并可避免癌细胞转移。但是，临床用卟啉类光敏剂所需的激活光组织穿透深度浅，限制了光动力疗法适应症范围。本项目针对上述问题，拟在Yb3+敏化体系中引入新的敏化离子，减小上转化发光激发光与水分子吸收的重叠，有效降低激发光的组织热损伤；另一方面，通过纳米颗粒表面修饰光敏剂构建受上转换发光调控的纳米光敏药物，并与抗体耦联实现肿瘤特异性的上转换光学成像与治疗一体化功能，并发展上述探针的体内应用方法。

中文关键词： 稀土纳米晶体；上转换发光；低热损伤；分子探针；光动力治疗

英文摘要： Accurately localizing and effectively treating tumors, have become the basic scientific questions facing cancer research. The upconversion luminescent (UCL) imaging based on rare earth nanocrystals, could integrate the high sensitivity of optical imaging with the advantages of UCL, such as great penetration depth and no auto-fluorescence. However, the currently used sensitizer Yb3+ has only one excited state, which result in narrow absorption band located at ca. 980 nm, coinciding with the strong absorption of water. Therefore, continuous laser irradiation at 980 nm to trigger the UCL process would lead to a risk of local temperature rise, and substantial overheating may even induce tissue damages. On the other hand, photodynamic therapy as a new technology to treat tumor not only has several advantages, such as minimal trauma, low toxicity, high selectivity and security, but also can prevent metastasis. However, the photosensitizers in clinical treatments are excited by visible light, which has limited penetration depth, resulting in ineffective therapeutic effects to internal tumors. This proposal intends to address these challenges, by introducing Nd3+ as a new near-infrared absorbers and sensitizers in the conventional Yb3+-doped upconversion luminescent nanocrystals to extend the excitation from 980 nm to 808 nm. In the mean time, by attaching the photosensitizer and tumor specific antibody to the nanoparticles, we also propose to develop the theranostic agent for both contrast: upconversion luminescent imaging and photodynamic therapy, and explore the in vivo application methods for the above probe.

英文关键词： rare earth nanocrystal;upconversion luminescence;low thermal damage;molecular probes;photodynamic therapy