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用于肿瘤成像和治疗的磁性纳米粒子:一种所谓的治疗诊断系统。

Magnetic nanoparticles for tumor imaging and therapy: a so-called theranostic system.

机构信息

School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.

出版信息

Pharm Res. 2013 Oct;30(10):2445-58. doi: 10.1007/s11095-013-0982-y. Epub 2013 Jan 24.

Abstract

In this review, we discussed the establishment of a so-called "theranostic" system by instituting the basic principles including the use of: [1] magnetic iron oxide nanoparticles (MION)-based drug carrier; [2] intra-arterial (I.A.) magnetic targeting; [3] macromolecular drugs with unmatched therapeutic potency and a repetitive reaction mechanism; [4] cell-penetrating peptide-mediated cellular drug uptake; and [5] heparin/protamine-regulated prodrug protection and tumor-specific drug re-activation into one single drug delivery system to overcome all possible obstacles, thereby achieving a potentially non-invasive, magnetic resonance imaging-guided, clinically enabled yet minimally toxic brain tumor drug therapy. By applying a topography-optimized I.A. magnetic targeting to dodge rapid organ clearance of the carrier during its first passage into the circulation, tumor capture of MION was enriched by >350 folds over that by conventional passive enhanced permeability and retention targeting. By adopting the prodrug strategy, we observed by far the first experimental success in a rat model of delivering micro-gram quantity of the large β-galactosidase model protein selectively into a brain tumor but not to the ipsi- or contra-lateral normal brain regions. With the therapeutic regimens of most toxin/siRNA drugs to fully (>99.9%) eradicate a tumor being in the nano-molar range, the prospects of reaching this threshold become practically accomplishable.

摘要

在这篇综述中,我们讨论了通过建立所谓的“治疗诊断一体化”系统,将以下基本原则付诸实践:[1] 基于磁性氧化铁纳米粒子(MION)的药物载体;[2] 经动脉(IA)磁靶向;[3] 具有无与伦比的治疗效力和重复反应机制的大分子药物;[4] 细胞穿透肽介导的细胞内药物摄取;以及[5] 肝素/鱼精蛋白调控的前药保护和肿瘤特异性药物再激活,将所有可能的障碍纳入单一药物输送系统,从而实现潜在的非侵入性、磁共振成像引导、临床可行且最小毒副作用的脑肿瘤药物治疗。通过应用地形优化的 IA 磁靶向来规避载体在首次进入循环时的快速器官清除,MION 的肿瘤捕获比传统的被动增强通透性和保留靶向富集了>350 倍。通过采用前药策略,我们在大鼠脑肿瘤模型中观察到迄今为止的第一个实验成功,即选择性地将微克数量的大型β-半乳糖苷酶模型蛋白递送到脑肿瘤中,而不是同侧或对侧正常脑区。由于大多数毒素/siRNA 药物的治疗方案要完全(>99.9%)消除肿瘤,其治疗效果在纳摩尔范围内,达到这一阈值的前景变得切实可行。

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本文引用的文献

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Brain tumor targeting of magnetic nanoparticles for potential drug delivery: effect of administration route and magnetic field topography.
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