Purpose: To assess the ability of magnetic albumin nanospheres conjugated with folate (FA-MAN) to provide FR-specific enhancement of C6 glioblastoma on magnetic resonance (MR) images.

Procedures: Active targeting effect of magnetic albumin nanospheres conjugated with folate (FA-MAN) was evaluated based on MR images and histopathological analysis. MR imaging of subcutaneously transplanted C6 glioblastomas was performed after intravenous injection of FA-MAN, non-targeted (magnetic albumin nanospheres, MAN) and FA-inhibited (magnetic albumin nanospheres conjugated with folate plus folate, FA-MAN + FA) agents at designated time points. The T₂ relaxation times in tumors were compared among different treatment groups and were correlated with histopathological findings. Prussian blue staining and in vivo toxicology assay were also performed simultaneously.

Results: Upon MR imaging in vivo, T₂ relaxation time of the tumor sites in the group administrated with FA-MAN (T₂ is 49 ms, 46 ms and 45 ms at 24 h, 48 h and 72 h, respectively) has statistical difference compared to those in the groups of MAN (T₂ is 56 ms, 56 ms and 61 ms at 24 h, 48 h and 72 h, respectively) and FA-MAN + FA nanospheres (T₂ is 56 ms, 57 ms and 56 ms at 24 h, 48 h and 72 h, respectively). Prussian blue-stained results demonstrated that more iron particles accumulated in the tumors of the targeted group than those of the other groups. Toxicology assay showed that no noticeable body weight losses were observed after monitoring 31 days, and the results of routine blood parameters, liver and kidney function biomarkers also demonstrated that the nanoshperes did not influence the respectively physiological index. Besides, no obvious pathological injuries on the major organs were examined.

Conclusion: Folate-conjugated magnetic albumin nanospheres were more effective in targeting C6 glioblastoma in vivo.

目的：评估与叶酸偶联的磁性白蛋白纳米球（FA-MAN）在磁共振（MR）图像上提供FR特异性增强C6胶质母细胞瘤的能力。

程序：基于MR图像和组织病理学分析评估了与叶酸（FA-MAN）共轭的磁性白蛋白纳米球的主动靶向作用。在指定位置静脉注射FA-MAN，非靶向（磁性白蛋白纳米球，MAN）和FA抑制（磁性白蛋白纳米球与叶酸加叶酸，FA-MAN + FA）结合后，对皮下移植的C6胶质母细胞瘤进行MR成像时间点。比较不同治疗组之间肿瘤中的T ₂弛豫时间，并将其与组织病理学发现相关。同时进行普鲁士蓝染色和体内毒理学测定。

结果：在体内进行MR成像后，FA-MAN给药组中肿瘤部位的T ₂弛豫时间（T ₂在24 h，48 h和72 h分别为49 ms，46 ms和45 ms）具有统计学意义与MAN组（T ₂在24 h，48 h和72 h分别为56 ms，56 ms和61 ms）和FA-MAN + FA纳米球（T ₂分别在24小时，48小时和72小时分别为56 ms，57 ms和56 ms）。普鲁士蓝染色的结果表明，与其他组相比，靶向组肿瘤中积累的铁颗粒更多。毒理学分析表明，监测31天后未观察到明显的体重减轻，常规血液参数，肝和肾功能生物标志物的结果还表明，纳米级麻醉剂不会影响相应的生理指标。此外，未检查主要器官的明显病理损伤。

结论：叶酸偶联的磁性白蛋白纳米球在体内靶向C6胶质母细胞瘤更有效。