Asn-Gly-Arg-modified polydopamine-coated nanoparticles for dual-targeting therapy of brain glioma in rats.
Asn-Gly-Arg-modified polydopamine-coated nanoparticles for dual-targeting therapy of brain glioma in rats.
复制标题
Asn-Gly-Arg 修饰的聚多巴胺涂层纳米粒子用于大鼠脑胶质瘤的双重靶向治疗
DOI：
10.18632/oncotarget.12047
复制
发表时间：
2016-11-08
期刊：
影响因子：
--
通讯作者：
Cheng Y
中科院分区：
文献类型：
--
作者：
Hu J;Zhang X;Wen Z;Tan Y;Huang N;Cheng S;Zheng H;Cheng Y
血脑屏障（BBB）是脑胶质瘤化疗的主要临床障碍。在这里，我们合成了一种pH敏感的双靶向阿霉素（DOX）载体，以损害肿瘤内皮细胞，增强血脑屏障运输，并改善药物在胶质瘤细胞中的积累。药物递送系统由聚多巴胺（PDA）涂覆的介孔二氧化硅纳米颗粒（NPs，MSNs）构建，并且PDA涂层用Asn-Gly-Arg（NGR）官能化，所述Asn-Gly-Arg（NGR）是对分化簇13（CD 13）具有特异性亲和力的配体。与非靶向纳米粒（MSN-DOX-PDA）相比，MSN-DOX-PDA-NGR在体外培养的原代脑毛细血管内皮细胞（BCECs）和C6细胞中有更高的细胞内蓄积，并具有更高的血脑屏障通透性。体外和体内试验表明，MSN-DOX-PDA-NGR在颅内肿瘤组织中的蓄积高于未修饰的NPs。MSN-DOX-PDA-NGR的抗血管生成和抗肿瘤作用均强于MSN-DOX-PDA。因此，这些结果表明双靶向载体在脑胶质瘤治疗中是潜在有用的。
The blood-brain barrier (BBB) is the major clinical obstacle in the chemotherapeutic management of brain glioma. Here we synthesized a pH-sensitive dual-targeting doxorubicin (DOX) carrier to compromise tumor endothelial cells, enhance BBB transportation, and improve drug accumulation in glioma cells. The drug delivery system was constructed with polydopamine (PDA)-coated mesoporous silica nanoparticles (NPs, MSNs) and the PDA coating was functionalized with Asn-Gly-Arg (NGR), a ligand with specific affinity for cluster of differentiation 13 (CD13). MSN-DOX-PDA-NGR showed a higher intracellular accumulation in primary brain capillary endothelial cells (BCECs) and C6 cells and greater BBB permeability than the non-targeting NPs (MSN-DOX-PDA) did in vitro. Ex vivo and in vivo tests showed that MSN-DOX-PDA-NGR had a higher accumulation in intracranial tumorous tissue than the undecorated NPs did. Furthermore, the antiangiogenesis and antitumor efficacy of MSN-DOX-PDA-NGR were stronger than that of MSN-DOX-PDA. Therefore, these results indicate that the dual-targeting vehicles are potentially useful in brain glioma therapy.