胶质瘤是最常见的脑内肿瘤，研究表明完全切除肿瘤并尽量保留正常脑组织可改善患者预后，但目前MR成像难以精准界定肿瘤边界致手术无法彻底切除，且药物难以靶向递送至肿瘤细胞，因此亟需新的诊疗策略。我们前期研究发现：乳铁蛋白(Lf)修饰的MR/荧光纳米复合物可作脑胶质瘤的靶向性双模态对比剂；COPB2基因是胶质瘤中潜在新型预后和治疗靶点。据此提出构建Lf修饰的兼siRNA靶向传递与MR/荧光双模态成像的诊疗一体化纳米探针，拟①通过以氧化还原响应性的PEG-ss-PEI为纳米载体，以T2成像的SPIO纳米粒为MRI对比剂，以灵敏度高的Cy5.5为荧光染料，来实现高分辨率及高灵敏度的MR/荧光双模态成像；②以Lf为脑胶质瘤靶向分子，载入siRNA特异性沉默胶质瘤COPB2表达来实现胶质瘤的靶向基因治疗，并探究其与细胞凋亡的相关性。本项目为胶质瘤术前和术中精准诊断提供手段，为其精准治疗提供新方向。

Glioma is the most common intracerebral tumor. Studies have shown that complete resection of the tumor and preservation of normal brain tissue can improve the prognosis of patients. However, at present, MR imaging is difficult to accurately define the tumor boundary, limiting the complete removal of the tumor by surgery. And it is difficult to targeted delivery the drug to the tumor cells. Therefore, it is urgent to find a new diagnosis and treatment strategy. Our previous study found that lactoferrin (Lf) modified MRI / fluorescent nanocomplexes can be used as targeted bimodal contrast agents for gliomas, and the COPB2 gene is a potential new prognosis and therapeutic target for glioma. Based on this, we propose to construct an Lf-modified integrated theranostic nanoprobe with siRNA targeted delivery and MR / fluorescence dual-modality imaging. ① In this project, the high-resolution and high-sensitivity MR / fluorescence dual-mode imaging was achieved by selecting redox-responsive PEG-ss-PEI as nanocarriers, SPIO nanoparticles with T2 imaging as MRI contrast agent, and Cy5.5 with high sensitivity as fluorescent dyes. ② Lf is used as a glioma targeting molecule, and siRNA was loaded to specifically silence COPB2 expression to achieve targeted gene therapy in glioma, and explore its correlation with apoptosis. This project will provide means for preoperative and intraoperative accurate diagnosis, and provide innovative directions for the precise treatment of glioma.