Imaging the delivery of brain-penetrating PLGA nanoparticles in the brain using magnetic resonance.
Imaging the delivery of brain-penetrating PLGA nanoparticles in the brain using magnetic resonance.
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DOI：
10.1007/s11060-014-1658-0
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发表时间：
2015-02
影响因子：
3.9
通讯作者：
Zhou, Jiangbing
中科院分区：
文献类型：
--
作者：
Strohbehn, Garth;Coman, Daniel;Han, Liang;Ragheb, Ragy R. T.;Fahmy, Tarek M.;Huttner, Anita J.;Hyder, Fahmeed;Piepmeier, Joseph M.;Saltzman, W. Mark;Zhou, Jiangbing
目前对多形性胶质母细胞瘤（GBM）的治疗在很大程度上是无效的，几乎普遍的肿瘤复发。目前治疗的失败主要是由于缺乏有效递送治疗剂以扩散脑中的肿瘤的方法。在我们之前的研究中，我们开发了脑穿透纳米颗粒，当通过对流增强递送（CED）给药时，其能够穿透脑组织并分布在临床相关体积上。我们证明了这些颗粒能够有效地将化疗药物递送到脑中的弥漫性肿瘤，这表明它们可以作为治疗GBM的突破性方法。在最初的研究中，使用正电子发射断层扫描（PET）对大脑中的纳米颗粒进行成像。然而，该递送平台的临床转化可以通过使用磁共振成像（MRI）设计非侵入性检测模态来实现。为此，在这项研究中，我们开发了化学将超顺磁性氧化铁（SPIO）纳入脑穿透纳米颗粒。我们证明，SPIO负载的纳米粒子，它保持相同的形态纳米粒子没有SPIO，具有优异的横向（T2）弛豫。在CED之后，纳米颗粒在脑中的分布（即，在注射部位附近），并且负载SPIO的脑穿透纳米颗粒的持久信号衰减持续超过一个月的时间过程。这些纳米颗粒的开发是重要的，因为在未来的临床应用中，SPIO负载的纳米颗粒的共同施用将允许术中监测脑中的颗粒分布，以确保负载药物的纳米颗粒到达肿瘤，以及监测随时间的治疗益处并评估肿瘤复发模式。
Current therapy for glioblastoma multiforme (GBM) is largely ineffective, with nearly universal tumor recurrence. The failure of current therapy is primarily due to the lack of approaches for the efficient delivery of therapeutics to diffuse tumors in the brain. In our prior study, we developed brain-penetrating nanoparticles that are capable of penetrating brain tissue and distribute over clinically relevant volumes when administered via convection-enhanced delivery (CED). We demonstrated that these particles are capable of efficient delivery of chemotherapeutics to diffuse tumors in the brain, indicating that they may serve as a groundbreaking approach for the treatment of GBM. In the original study, nanoparticles in the brain were imaged using positron emission tomography (PET). However, clinical translation of this delivery platform can be enabled by engineering a non-invasive detection modality using magnetic resonance imaging (MRI). For this purpose, in this study, we developed chemistry to incorporate superparamagnetic iron oxide (SPIO) into the brain-penetrating nanoparticles. We demonstrated that SPIO-loaded nanoparticles, which remain the same morphology as nanoparticles without SPIO, have an excellent transverse (T2) relaxivity. After CED, the distribution of nanoparticles in the brain (i.e., in the vicinity of injection site) can be detected using MRI and the long-lasting signal attenuation of SPIO-loaded brain-penetrating nanoparticles lasted over a one-month timecourse. Development of these nanoparticles is significant as, in future clinical applications, co-administration of SPIO-loaded nanoparticles will allow for intraoperative monitoring of particle distribution in the brain to ensure drug-loaded nanoparticles reach tumors as well for monitoring the therapeutic benefit with time and to evaluate tumor relapse patterns.
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影响因子：
3.3
作者：
Ragheb, Ragy R. T.;Kim, Dongin;Bandyopadhyay, Arunima;Chahboune, Halima;Bulutoglu, Beyza;Ezaldein, Harib;Criscione, Jason M.;Fahmy, Tarek M.
通讯作者：
Fahmy, Tarek M.
影响因子：
3.7
作者：
Cerami E;Demir E;Schultz N;Taylor BS;Sander C
通讯作者：
Sander C
影响因子：
14.9
作者：
Benita Y;Kikuchi H;Smith AD;Zhang MQ;Chung DC;Xavier RJ
通讯作者：
Xavier RJ
影响因子：
11.2
作者：
Hadjipanayis CG;Machaidze R;Kaluzova M;Wang L;Schuette AJ;Chen H;Wu X;Mao H
通讯作者：
Mao H
DOI：
10.1126/science.1164382
发表时间：
2008-09-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Parsons DW;Jones S;Zhang X;Lin JC;Leary RJ;Angenendt P;Mankoo P;Carter H;Siu IM;Gallia GL;Olivi A;McLendon R;Rasheed BA;Keir S;Nikolskaya T;Nikolsky Y;Busam DA;Tekleab H;Diaz LA Jr;Hartigan J;Smith DR;Strausberg RL;Marie SK;Shinjo SM;Yan H;Riggins GJ;Bigner DD;Karchin R;Papadopoulos N;Parmigiani G;Vogelstein B;Velculescu VE;Kinzler KW
通讯作者：
Kinzler KW