低热效应近红外荧光成像/pH激活式光动力治疗诊疗一体化上转换纳米探针的构建与应用

项目名称： 低热效应近红外荧光成像/pH激活式光动力治疗诊疗一体化上转换纳米探针的构建与应用

项目编号： No.21505104

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 高分子科学

项目作者： 申纪伟

作者单位： 西北大学

项目金额： 21万元

中文摘要： 基于稀土上转换纳米粒子（UCNPs）的光学成像/光动力治疗（PDT）诊疗一体化纳米探针在重大疾病（如肿瘤）诊疗中具有良好的应用潜力。本项目旨在通过掺杂和核壳结构制备在980 和 800 nm光源激发下分别发射强近红外荧光和强绿色-红色荧光的UCNPs，并通过将分别与绿色和红色上转换荧光匹配的两种光敏剂共价修饰到UCNPs表面，构建兼具近红外光高组织穿透能力、PDT过程热效应低和成像过程不产生单线态氧特性的光学成像/PDT诊疗一体化纳米探针；然后利用pH响应性酯键将良好生物相容性配体连接到探针表面，实现光敏剂与治疗目标间距离的调控，开发PDT过程需要肿瘤低pH微环境触发酯键断裂、拉近光敏剂与治疗目标间距离才能实现的纳米探针；通过靶向分子铃蟾肽类似物的修饰构建良好生物相容性的靶向性近红外荧光成像/PDT诊疗一体化纳米探针。本项目对诊疗一体化上转换纳米探针诊疗效率和安全性的提高具有重要意义。

中文关键词： 诊疗一体化纳米探针；上转换；近红外成像；低过热效应；pH激活式光动力治疗

英文摘要： Theranostic nanoprobe integrated optical bioimaging and photodynamic therapy (PDT) capacity based on rare-earth upconversion nanoparticles (UCNPs) show great potential for theranostic application of malignant diseases (such as cancer). The aim of this project is to develop theranostic upconversion nanoprobe with independent strong near-infrared emitting and strong green-red emitting under 980 nm laser excitation and 800 nm laser excitation separately for deep-tissue bioimaging without singlet oxygen generation and PDT with minimized overheating irradiation in vivo by doping and core-shell nanoparticle design, to develop pH-thriggered theranostic nanoprobe by assembling covelently two photosensitizers matched with green-red fluorescence through EDC/NHS coupling strategy and coating biological surface ligand through pH-triggered ester bond to the surface of theranostic UCNPs in succession, to develop biocompatibe and tumor targeted theranostic probe for near-infrared fluorescent bioimaging/pH triggered PDT. This project will promote the efficiency and safety of theranostic upconversion nanoprobe.

英文关键词： theranostic nanoprobe;upconversion;near-infrared imaging;minimized overheating irradiation;pH-triggered PDT