Kuo Yung-Chih, Wang I-Hsin
a Department of Chemical Engineering , National Chung Cheng University , Chia-Yi , Taiwan , Republic of China.
J Drug Target. 2016 Aug;24(7):645-54. doi: 10.3109/1061186X.2015.1132223. Epub 2016 Jan 15.
Melanotransferrin antibody (MA) and tamoxifen (TX) were conjugated on etoposide (ETP)-entrapped solid lipid nanoparticles (ETP-SLNs) to target the blood-brain barrier (BBB) and glioblastom multiforme (GBM). MA- and TX-conjugated ETP-SLNs (MA-TX-ETP-SLNs) were used to infiltrate the BBB comprising a monolayer of human astrocyte-regulated human brain-microvascular endothelial cells (HBMECs) and to restrain the proliferation of malignant U87MG cells. TX-grafted ETP-SLNs (TX-ETP-SLNs) significantly enhanced the BBB permeability coefficient for ETP and raised the fluorescent intensity of calcein-AM when compared with ETP-SLNs. In addition, surface MA could increase the BBB permeability coefficient for ETP about twofold. The viability of HBMECs was higher than 86%, suggesting a high biocompatibility of MA-TX-ETP-SLNs. Moreover, the efficiency in antiproliferation against U87MG cells was in the order of MA-TX-ETP-SLNs > TX-ETP-SLNs > ETP-SLNs > SLNs. The capability of MA-TX-ETP-SLNs to target HBMECs and U87MG cells during internalization was verified by immunochemical staining of expressed melanotransferrin. MA-TX-ETP-SLNs can be a potent pharmacotherapy to deliver ETP across the BBB to GBM.
将黑素转铁蛋白抗体（MA）和他莫昔芬（TX）偶联到包载依托泊苷（ETP）的固体脂质纳米粒（ETP-SLNs）上，以靶向血脑屏障（BBB）和多形性胶质母细胞瘤（GBM）。MA和TX偶联的ETP-SLNs（MA-TX-ETP-SLNs）用于穿透由人星形胶质细胞调节的人脑微血管内皮细胞（HBMECs）单层组成的血脑屏障，并抑制恶性U87MG细胞的增殖。与ETP-SLNs相比，TX接枝的ETP-SLNs（TX-ETP-SLNs）显著提高了ETP的血脑屏障渗透系数，并提高了钙黄绿素-AM的荧光强度。此外，表面MA可使ETP的血脑屏障渗透系数增加约两倍。HBMECs的活力高于86%，表明MA-TX-ETP-SLNs具有高生物相容性。此外，对U87MG细胞的抗增殖效率顺序为MA-TX-ETP-SLNs＞TX-ETP-SLNs＞ETP-SLNs＞SLNs。通过对表达的黑素转铁蛋白进行免疫化学染色，验证了MA-TX-ETP-SLNs在内化过程中靶向HBMECs和U87MG细胞的能力。MA-TX-ETP-SLNs可以作为一种有效的药物疗法，将ETP通过血脑屏障递送至GBM。
