半胱胺及RE-1-RGD短肽修饰的稀土上转换发光纳米颗粒用于肿瘤诊疗一体的应用基础研究

Lanthanide upconversion nanoparticles (UCN) have highly potential application value in the fields like fluorescence imaging, tumor diagnosis and drug tracking, due to their deep incident, weak auto-fluorescence, low background, high sensitivity and well biocompatibility. Our group had reported autophagy-mediated chemosensitization by cysteamine (CS) in cancer cells.Additionally, lanthanide nanomaterials were proved to be able to induce pro-death autophagy, and coating of RE-1 peptide could modulate the autophagy-inducing capacity and toxicity of lanthanide materials effectively. The proposing project will innovatively link tumor targeting sequence (RGD) and cysteamine to UCN through specific binding peptide (RE-1) in our previous work, in order to improve the ability of tumor imaging and tumor killing of the muti-functional material through the function of "RGD" targeting, and preliminarily realize the integration of diagnosis and therapy. The further investigation of this project will provide theoretical basis and research method for a wider and more precise application of lanthanide upconversion luminescence nanoparticles in the field of tumor diagnosis and therapy.

稀土上转换发光纳米颗粒（UCN）因具有入射深、自发荧光弱、背景噪音小且敏感度高，生物相容性好等优点，而在荧光成像、肿瘤诊断及药物追踪等领域具有广泛的应用前景和价值。项目组前期工作显示，半胱胺（CS）具有通过诱导细胞自噬增强肿瘤细胞对化疗药物敏感性的功能。另外，稀土纳米材料也被项目组证明具有诱导促细胞死亡型自噬的能力并且RE-1包裹肽能有效调控稀土纳米材料的自噬诱导能力及毒性。本项目利用课题组前期工作基础，通过UCN特异结合短肽RE-1将肿瘤靶向多肽RGD及CS连接到UCN上，形成新型多功能生物医用纳米材料，进一步研究该材料的肿瘤组织靶向能力（RGD组分）、成像能力（UCN组分）及其化疗增敏的效力(CS组分)，初步实现诊疗一体化的理想目标。本课题的开展将为稀土上转换发光纳米颗粒在肿瘤诊断及治疗领域更广泛、更精确的应用提供理论基础和研究方法。

稀土上转换发光纳米颗粒（UCN）因具有入射深、自发荧光弱、背景噪音小且敏感度高，生物相容性好等优点，而在荧光成像、肿瘤诊断及药物追踪等领域具有广泛的应用前景和价值。项目组前期工作显示，半胱胺（CS）具有通过诱导细胞自噬增强肿瘤细胞对化疗药物敏感性的功能。另外，稀土纳米材料也被项目组证明具有诱导促细胞死亡型自噬的能力并且RE-1包裹肽能有效调控稀土纳米材料的自噬诱导能力及毒性。本项目利用课题组前期工作基础，通过UCN特异结合短肽RE-1将肿瘤靶向多肽RGD及CS连接到UCN上，形成新型多功能生物医用纳米材料，进一步研究该材料的肿瘤组织靶向能力（RGD组分）、成像能力（UCN组分）及其化疗增敏的效力(CS组分)，初步实现诊疗一体化的理想目标。项目按照任务书要求，在本项目的资助下，我们主要围绕着纳米材料肿瘤诊疗一体这一核心，针对项目任务书的研究目标和拟解决的关键科学问题，我们按照研究计划基本完成了预期研究结果。共发表SCI论文7篇，培养博士研究生4名。