基于稀土上转换纳米材料的复合纳米诊/疗试剂的构建与评价

How to improve the therapeutic effect of photodynamic therapy become one focus of researchers，improving the penetration depth of the excitation light is one of the solutions. Comparing withβ-NaYF4:Yb3+,Er3+, lanthanide oxysulfides upconversion nanomaterials can emit strong red light under the excitation of 980 nm when doping with the same amounts of Yb3+,Er3+ ions, indicating that lanthanide oxysulfides have more potential to be used in photodynamic therapy as the carriers of photosensitizer. Researchers, however, haven’t paid much attention on the synthesis and applications of lanthanide oxysulfides nanomaterials. This project is proposed to prepare multifunctional Gd2O2S:Ln3+(Ln3+=Yb3+,Er3+)/Ce6( or DOX) theranostic nanoagents using Gd2O2S:Ln3+(Ln3+=Yb3+,Er3+) up conversion nanomaterials as carriers, which can be controllable synthesis by adjusting the synthesis method and reaction condition, followed by introduction of photosensitizer Ce6(or anticancerogen DOX) on the oxysulfides carrier through modification of composition and surface structures. The methods to improve the tumor targeting and membrane penetration of the nanoagents also will be studied in this project. The photodynamic therapy effects, fluorescent labeling properties and therapy function of the theranostic nanoagents will be investigated after the system biological evaluation. The proposed work will provide important experimental data for controllable synthesis and potential application in the field of biomedicine of lanthanide oxysulfides nanomaterials, having research significance and important medical value.

如何提高光动力学治疗效果是亟待解决的问题，提高照射光的穿透深度是解决方法之一。就相同的Yb3+,Er3+掺杂量，在980 nm激发下，稀土硫氧化物可发出明亮的红光，较以绿光为主的β-NaYF4:Yb3+,Er3+，更有望以光敏剂载体的形式应用到光动力学治疗。然而，相关的研究还未引起人们的关注。本项目拟选用Gd2O2S为基质材料，通过控制反应条件合成分散性好，形貌可控的Gd2O2S:Ln3+(Ln3+=Yb3+,Er3+)纳米材料，对其进行处理，负载光敏剂Ce6（或抗癌药DOX），合成Gd2O2S:Ln3+(Ln3+=Yb3+,Er3+)/Ce6（或DOX）复合纳米诊/疗试剂，提高试剂的肿瘤靶向性和膜穿透性。进行系统的生物评价后对试剂的光动力学治疗及诊/疗功能进行研究。本项目的开展将为稀土硫氧化物纳米材料的可控合成及其在生物医学领域中的潜在应用提供实验依据，具有重要的研究意义和医学价值。

众所周知，提高照射光的穿透深度是提高光学治疗效果的方法之一。就相同的Yb3+,Er3+掺杂量，在980 nm激发下，稀土硫氧化物可发出明亮的红光，较以绿光为主的β-NaYF4: Yb3+,Er3+，更有望以光敏剂载体或光热试剂的形式应用到光动力学治疗等光学治疗领域。然而，相关的研究还未引起人们的关注。本项目选用Gd2O2S:Ln3+(Ln3+=Yb3+,Er3+)上转换纳米材料为主要研究对象，采用多种合成方法，通过控制反应条件合成分散性好，形貌可控且亲水的Gd2O2S:Ln3+(Ln3+=Yb3+,Er3+)上转换纳米管，Gd2O2S:Ln3+(Ln3+=Yb3+,Er3+)上转换纳米粒子，及包覆在介孔碳纳米粒子（mC）上的Gd2O2S:Ln3+(Ln3+=Yb3+,Er3+)上转换纳米粒子，研究材料的光学性质，相关影响因素，对材料的生物相容性进行评价。之后采用了物理吸附法、介孔二氧化硅封装法等，包覆在介孔碳上等多种功能材料负载方法，将光敏剂Ce6和抗癌药DOX负载在上述纳米材料载体上，构建了Gd2O2S:Ln3+(Ln3+=Yb3+,Er3+)@Ce6，Gd2O2S:Ln3+(Ln3+=Yb3+,Er3+)@SiO2@mSiO2@DOX, Gd2O2S:Ln3+(Ln3+=Yb3+,Er3+)@mC@DOX 三种复合纳米材料。探索在保证功能材料的功能活性前提下提高材料负载量的新方法，对所得复合纳米诊/疗试剂进行系统的体外细胞评价，建立动物肿瘤模型，对其光学治疗及诊/疗功能进行评价，对试剂在体内的代谢分布情况进行研究。这些实验结果为稀土硫氧化物及含有稀土硫氧化物的复合纳米试剂在生物医学领域中的潜在应用做铺垫，拓宽稀土硫氧化物类纳米材料的应用提供实验依据，具有重要的研究意义和医学价值。