Angiopep-2介导的双靶向纳米载体研究及其在大鼠C6胶质瘤MR显像中的价值

目的 制备Angiopep-2介导的双靶向纳米载体对比剂,并从细胞和动物水平评估其在胶质瘤显像的中价值。方法 制备无和有Ang包裹的聚N,N-二乙基丙烯酰胺纳米对比剂(NP、Ang-NP)。分别测定C6和BCEs与NP、Ang-NP共培养不同时间的荧光强度；C6细胞球对Ang-NP摄取率和竞争抑制实验；对C6胶质瘤大鼠模型行Ang-NP-Gd和DOTA-Gd增强扫描,比较两组肿瘤的CNR及对肿瘤边界显示情况。结果C6细胞及血管内皮细胞对Ang-NP-FITC均有明显的摄取；C6肿瘤球对三组摄取率顺序为：Ang-NP＞NP＞Ang-NP Angiopep-2；Ang-NP-Gd显示肿瘤边界较DOTA-Gd更清晰；CNR随时间增大,在12 h达峰值。结论Angiopep-2与血管内皮细胞及胶质瘤细胞的低密度脂蛋白受体相关蛋白-1受体结合,具有很强的穿透血脑屏障及进入脑胶质瘤的能力。

Angiopep-2 mediated dual-targeting nanoparticle carrier and its value on magnetic resonance imaging of C6 glioma rat

Objective Prepare Angiopep-2 mediated dual-targeting nanoparticle and explore the targeting ability at a cellular level and in animals. Methods C6 cells and endothelial cells were incubated with Ang-NP-FITC and NP-FITC at different time, and assay the fluorescence intensity. The uptake of C6 glioma spheroids to Ang-NP and its competitive inhibition were observed with flow cytometry. Ang-NP-Gd or NP-Gd respectively was injected in rat C6 glioma model, the CNR of tumors were measured and compared between two groups, the boundary of tumors were compared. Results The uptake of C6 cells and endothelial cells to Ang-NP-FITC was obvious . The order of fluorescence intensity of C6 glioma spheroids was Ang-NP-FITC, NP-FITC and Ang-NP-FITC+Angiopep-2 in descending order. With Ang-NP-Gd enhancement, the boundary of tumors was more clear, CNR was increased by time and reached the top at 12 h. Conclusion The nanoparticles contrast agent modified with Angiopep-2 specific bind of low density lipoprotein receptor related protein-1 receptor, and has very strong ability to penetrate the BBB and enter the brain glioma location.