The transport of non-surfactant based paclitaxel loaded magnetic nanoparticles across the blood brain barrier in a rat model
The transport of non-surfactant based paclitaxel loaded magnetic nanoparticles across the blood brain barrier in a rat model
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DOI：
10.1016/j.biomaterials.2011.12.046
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发表时间：
2012-04-01
期刊：
影响因子：
14
通讯作者：
Sahoo, Sanjeeb Kumar
中科院分区：
文献类型：
--
作者：
Dilnawaz, Fahima;Singh, Abhalaxmi;Sahoo, Sanjeeb Kumar
利用磁性纳米粒子的固有特性进行医学诊断治疗是一个非常有意义的研究课题。为了开发潜在的胶质瘤治疗药物，研究了水分散紫杉醇负载的MNP（Pac-MNP）在胶质母细胞瘤细胞系（U-87）中的功效。在U-87细胞中使用GPNMB缀合的Pac-MNP主动靶向所鉴定的潜在受体，即胶质母细胞瘤细胞过表达的糖蛋白非转移性黑素瘤蛋白B（GPNMB）。由于血脑屏障（BBB）是胶质母细胞瘤治疗的主要障碍，因此，尝试评估Pac-MNP在大鼠体内的生物分布和脑摄取。Pac-MNP的生物利用度说明了体内延长的血液循环，这表明与天然紫杉醇相比，大鼠脑组织中存在显著量的药物。此外，透射电子显微镜（TEM）研究揭示了Pac-MNP在脑组织中的显著积累。作为组织水平磁共振成像（MRI）的有效对比增强剂，不含任何表面活性剂的MNP在肝脏和脑成像中表现出增强的对比效果。因此，药物在大鼠脑组织中的显著流行性、体外靶向潜力以及增强的对比效应引起了MNP用于脑肿瘤治疗的非侵入性评估和治疗诊断应用。(C)2011爱思唯尔有限公司版权所有。
There is much interest in utilizing the intrinsic properties of magnetic nanoparticles (MNPs) for the theranostic approaches in medicine. With an aim to develop a potential therapeutics for glioma treatment, efficacy of aqueous dispersible paclitaxel loaded MNPs (Pac-MNPs) were studied in glioblastoma cell line (U-87). The identified potential receptor, glycoprotein non-metastatic melanoma protein B (GPNMB) overexpressal by glioblastoma cells, was actively targeted using GPNMB conjugated Pac-MNPs in U-87 cells. As blood brain barrier (BBB) is the primary impediment in the treatment of glioblastoma, therefore, an attempt was taken to evaluate the biodistribution and brain uptake of Pac-MNPs in rats. The bioavailability of Pac-MNPs illustrated a prolonged blood circulation in vivo, which demonstrated the presence of significant amounts of drug in rat brain tissues as compared to native paclitaxel. Further, the transmission electron microscopy (TEM) study revealed significant accumulation of the Pac-MNPs in the brain tissues. Being an effective contrast enhancement agent for magnetic resonance imaging (MRI) at tissue levels, the MNPs devoid of any surfactant demonstrated enhanced contrast effect in liver and brain imaging. Hence, the significant prevalence of drugs in the rat brain tissues, in vitro targeting potentiality as well as the augmented contrast effect elicit the non-invasive assessment and theranostic applications of MNPs for brain tumor therapy. (C) 2011 Elsevier Ltd. All rights reserved.