部分甲状腺癌患者在治疗过程中出现核素治疗抵抗，而分子靶向治疗又存在毒副作用大及肿瘤耐药等问题。课题组前期研究表明，HSP90抑制剂17-AAG可明显抑制未分化甲状腺癌增殖，并可诱导其凋亡；纳米载体BSA-PCL高分子脂质体可有效实现多种药物的助溶、共载及肿瘤靶向性治疗（研究成果已发表于中华核医学与分子影像杂志及Nanoscale等杂志）。在此研究的基础上，我们拟构建一种新型的以甲状腺癌表面高表达的VEGF为靶向位点的三合一聚合纳米载体，将131I标记于17-AAG上，再与mTOR抑制剂Torin2共同包载于载体内，分析该共载纳米载体的粒径、载药量、靶向性、释药动力学及对甲状腺癌细胞的毒性作用；并建立荷瘤裸鼠模型，通过体内研究进一步分析该给药系统的可行性、安全性及协同抗肿瘤活性。本研究将先进的靶向性纳米技术与经典的131I治疗相结合，并将探讨分子靶向药物与核素联合治疗的可行性和高效性。

Some patients with differentiated thyroid cancer have poor prognosis because of occurrence of resistance to radioiodine therapy. Moreover, molecular targeted drugs have obvious side effects and might be prone to drug resistance. Our previous studies showed that 17-AAG, the prototypical HSP90 inhibitor, could restrain the proliferation of anaplastic thyroid cancer cells and induce apoptosis; BSA-PCL polymer liposomes could offer an effective nanotechnology platform for solubilization, co-loaded and targeted therapy of multiple drugs (research results have been published in Chin J Nucl Med Mol Imaging, Nanoscale, and so on). On the basis of these results, we plan to construct a new 3-in-1 BSA-PCL polymer liposomes targeting high expression of VEGF on the thyroid cancer cells’ surface, containing 131I-17-AAG and Torin2 (mTOR inhibitor). We will evaluate the dimensions, the level of drug loading, targeting, drug release kinetics and cytotoxicity of the nanoparticles (NP) to thyroid cancer cells. In addition, we shall perform preliminary animal experiments to verify the feasibility, safety and synergistic antineoplastic activity on this NP-based delivery which associating molecular targeted drugs with radioiodine. The research will combine advanced targeting nanotechnology with classic 131I therapy, investigate the feasibility and effectiveness of combination therapy of molecular targeted drugs with radionuclide.