131I耐药分化型甲状腺癌或未分化甲状腺癌的治疗，是目前临床核医学的难题。纳米材料近年来发展迅猛，包括本研究前期工作在内的诸多研究，均表明金属有机骨架材料（MOFs）以其设计的多样化、超大的比表面积、可调且丰富的孔径等独特优势，在生物医学领域尤其是药物递送方面具有重要价值，但是，MOFs在难治甲状腺癌诊疗一体化中的应用研究鲜有报道。本项目拟在MOFs上负载银离子用于吸附131I，通过修饰多肽RGD用以靶向131I耐药分化型甲状腺癌或未分化甲状腺癌表面过表达的整合素αvβ3，进一步在MOFs上负载小分子药物DOX或免疫增强剂R837，实现以MOFs为基础的多功能纳米探针的构建，通过细胞水平和小动物活体水平实验，研究其在难治甲状腺癌的核素治疗联合化疗或免疫治疗中的应用。本项目将开拓纳米材料在难治性甲状腺癌中的应用，对于难治性甲状腺癌诊疗一体化探针的构建和发展，有重要的科学价值和潜在临床价值。

Thyroid cancer is the most common malignancy in endocrine system. And 131I treatment is the most effective solution for post-surgical management of differentiated thyroid cancer (DTC). However, radioactive iodine refractory DTC (RAIR-DTC) or anaplastic thyroid cancer (ATC) has become a nuclear medicine therapeutic challenge owing to no definitely effective treatment yet. Recently, nano material has developed rapidly, and metal-organic frameworks (MOFs) have shown great potential in biomedicine, especially in drug delivery due to their diverse chemical composition, enormous specific surface area and abundant pores. In our preliminary work published in ACS Applied Materials & Interfaces, MOFs were proved to be superior carriers for drug delivery. Nevertheless, no work on fabrication of theranostic probes using MOFs to load 131I for RAIR-DTC or ATC has been reported so far. Herein, we aim to develop MOFs for targeting diagnosis and treatment of RAIR-DTC or ATC, loaded with elemental silver to adsorb 131I indirectly and modified with RGD peptide to target the integrin αvβ3 over-expressed on the surface of RAIR-DTC or ATC. Small molecular drugs can also be loaded on MOFs simultaneously such as chemotherapy drug DOX and immune agonist R837, to achieve radionuclide treatment accompanied with chemotherapy or immune therapy. In this study, reaction conditions will be optimized to prepare the optimal theranostic probe, such as silver loading capacity, 131I absorptive capacity, DOX or R837 loading capacity, and the probe will be characterized thoroughly. In the cell experiments, MTT, cellar SPECT/CT imaging (or 131I uptake assay) will be carried out to evaluate the toxicity in vitro, targeting imaging quality, radionuclide therapy or combination with chemotherapy/immune therapy efficacy. As for animal experiments, blood biochemistry, HE staining of organs, and ICP-MS test will be investigated to assess the toxicity in vivo. Tumor SPECT/CT imaging and tumor size monitoring will be performed to verify the tumor targeting imaging ability and radionuclide therapy or combination with chemotherapy/immune therapy effect in vivo. The project will promote further development of theranostic probes and exploration of new therapy for RAIR-DTC and ATC, which is of significant value both in scientific theory and potential clinical applications.