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增强传递的高分子纳米粒用于恶性脑胶质瘤的治疗及其体内成像。

Convection-enhanced delivery and in vivo imaging of polymeric nanoparticles for the treatment of malignant glioma.

机构信息

Section of Neurosurgery, Department of Surgery, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois, USA.

Department of Pathology, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois, USA.

出版信息

Nanomedicine. 2014 Jan;10(1):149-57. doi: 10.1016/j.nano.2013.07.003. Epub 2013 Jul 24.

Abstract

UNLABELLED

A major obstacle to the management of malignant glioma is the inability to effectively deliver therapeutic agent to the tumor. In this study, we describe a polymeric nanoparticle vector that not only delivers viable therapeutic, but can also be tracked in vivo using MRI. Nanoparticles, produced by a non-emulsion technique, were fabricated to carry iron oxide within the shell and the chemotherapeutic agent, temozolomide (TMZ), as the payload. Nanoparticle properties were characterized and subsequently their endocytosis-mediated uptake by glioma cells was demonstrated. Convection-enhanced delivery (CED) can disperse nanoparticles through the rodent brain and their distribution is accurately visualized by MRI. Infusion of nanoparticles does not result in observable animal toxicity relative to control. CED of TMZ-bearing nanoparticles prolongs the survival of animals with intracranial xenografts compared to control. In conclusion, the described nanoparticle vector represents a unique multifunctional platform that can be used for image-guided treatment of malignant glioma.

FROM THE CLINICAL EDITOR

GBM remains one of the most notoriously treatment-unresponsive cancer types. In this study, a multifunctional nanoparticle-based temozolomide delivery system was demonstrated to possess enhanced treatment efficacy in a rodent xenograft GBM model, with the added benefit of MRI-based tracking via the incorporation of iron oxide as a T2* contrast material in the nanoparticles.

摘要

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恶性神经胶质瘤治疗的主要障碍是无法将治疗剂有效递送至肿瘤。在本研究中,我们描述了一种聚合物纳米颗粒载体,它不仅可以输送有活力的治疗剂,还可以使用 MRI 在体内进行跟踪。通过非乳液技术生产的纳米颗粒被制成壳内携带氧化铁和化疗药物替莫唑胺(TMZ)作为有效载荷。对纳米颗粒的性质进行了表征,随后证明了它们通过内吞作用被神经胶质瘤细胞摄取。通过增强的输送(CED)可以将纳米颗粒分散到啮齿动物的大脑中,并通过 MRI 准确地可视化它们的分布。与对照相比,纳米颗粒的输注不会导致可观察到的动物毒性。与对照相比,CED 携带 TMZ 的纳米颗粒延长了颅内异种移植动物的存活时间。总之,所描述的纳米颗粒载体代表了一种独特的多功能平台,可用于恶性神经胶质瘤的图像引导治疗。

来自临床编辑

GBM 仍然是治疗反应最不明显的癌症类型之一。在这项研究中,证明了一种基于多功能纳米颗粒的替莫唑胺递送系统在啮齿动物异种移植 GBM 模型中具有增强的治疗效果,并且通过将氧化铁作为 T2*对比材料纳入纳米颗粒中,还具有基于 MRI 的跟踪的额外益处。

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