Kuo Yung-Chih, Chao In-Wei
Dept. of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan, 62102, Republic of China.
Biotechnol Prog. 2016 Mar;32(2):480-90. doi: 10.1002/btpr.2214. Epub 2015 Dec 31.
Solid lipid nanoparticles (SLNs) comprising complex internal lipids were conjugated with melanotransferrin antibody (MA) to carry anticancer etoposide across the blood-brain barrier (BBB) for managing glioblastoma multiforme (GBM). MA was crosslinked on the surface of etoposide-loaded SLNs (ETP-SLNs) to target human brain-microvascular endothelial cells (HBMECs) and U87MG cells. The experimental evidences showed that an increase in the tripalmitin weight percentage in lipids enhanced the particle size and viability of U87MG cells, however decreased the etoposide loading efficiency, MA conjugation efficiency, and permeability coefficient for etoposide across the BBB. A high level of MA on the particle surface increased the atomic ratio of nitrogen to phosphorus and permeability coefficient for propidium iodide and etoposide across the BBB, however reduced the MA conjugation efficiency, transendothelial electrical resistance, and viability of U87MG cells. Based on immunochemical staining, we found that MA on ETP-SLNs triggered the melanotransferrin-mediated transcytosis and promoted the growth-inhibitory efficacy to U87MG cells. MA-conjugated ETP-SLNs can be a promising colloidal delivery system for malignant GBM pharmacotherapy. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 32:480-490, 2016.
将包含复合内部脂质的固体脂质纳米粒（SLNs）与黑素转铁蛋白抗体（MA）偶联，以携带抗癌药物依托泊苷穿过血脑屏障（BBB），用于治疗多形性胶质母细胞瘤（GBM）。MA交联在负载依托泊苷的SLNs（ETP-SLNs）表面，以靶向人脑微血管内皮细胞（HBMECs）和U87MG细胞。实验证据表明，脂质中三棕榈酸甘油酯重量百分比的增加提高了U87MG细胞的粒径和活力，但降低了依托泊苷的负载效率、MA偶联效率以及依托泊苷穿过血脑屏障的渗透系数。颗粒表面高水平的MA增加了氮与磷的原子比以及碘化丙啶和依托泊苷穿过血脑屏障的渗透系数，但降低了MA偶联效率、跨内皮电阻和U87MG细胞的活力。基于免疫化学染色，我们发现ETP-SLNs上的MA触发了黑素转铁蛋白介导的转胞吞作用，并促进了对U87MG细胞的生长抑制效果。MA偶联的ETP-SLNs可能是一种用于恶性GBM药物治疗的有前景的胶体递送系统。© 2015美国化学工程师学会生物技术进展，32:480 - 490，2016。
