A New Interleukin-13 Amino-Coated Gadolinium Metallofullerene Nanoparticle for Targeted MRI Detection of Glioblastoma Tumor Cells
A New Interleukin-13 Amino-Coated Gadolinium Metallofullerene Nanoparticle for Targeted MRI Detection of Glioblastoma Tumor Cells
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DOI：
10.1021/jacs.5b03991
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发表时间：
2015-06-24
影响因子：
15
通讯作者：
Dorn, Harry C.
中科院分区：
文献类型：
--
作者：
Li, Tinghui;Murphy, Susan;Dorn, Harry C.
开发新的纳米颗粒作为下一代诊断和治疗（治疗诊断）药物平台是化学和癌症研究的一个活跃领域。尽管已经报道了许多含钆（Gd）的金属富勒烯作为诊断磁共振成像（MRI）造影剂，但在大多数情况下，金属富勒烯笼表面由带负电荷的羧基或羟基组成，其限制了与细胞表面的吸引力。据报道，具有正电荷的纳米颗粒将更有效地结合到带负电荷的磷脂双层细胞表面，并且将更容易经历内吞作用。本文报道了一种新型功能化三金属氮化物模板内嵌金属富勒烯（TNT EMF）的制备，Gd3N@C-80（OH）（x）（NH 2）（y），其笼状表面带有带正电的氨基（-NH3+）并直接将其与类似的羧基和羟基功能化衍生物进行比较。用X射线光电子能谱（XPS）、动态光散射（DLS）和红外光谱对该纳米粒子进行了表征。它具有优异的1H MR弛豫性能。先前的研究已经清楚地表明，细胞因子白细胞介素-13（IL-13）有效地靶向多形性胶质母细胞瘤（GBM）细胞，已知GBM细胞过表达IL-13 R α 2。我们还报道了这种氨基包被的Gd-纳米平台，当随后与白细胞介素-13肽IL-13-Gd3N@C-80（OH）（x）（NH 2）（y）缀合时，表现出增强的U-251 GBM细胞系的靶向，并且可以在原位GBM小鼠模型中有效地静脉内递送。
The development of new nanoparticles as next-generation diagnostic and therapeutic (theranostic) drug platforms is an active area of both chemistry and cancer research. Although numerous gadolinium (Gd) containing metallofullerenes as diagnostic magnetic resonance imaging (MRI) contrast agents have been reported, the metallofullerene cage surface, in most cases, consists of negatively charged carboxyl or hydroxyl groups that limit attractive forces with the cellular surface. It has been reported that nanoparticles with a positive charge will bind more efficiently to negatively charged phospholipid bilayer cellular surfaces, and will more readily undergo endocytosis. In this paper, we report the preparation of a new functionalized trimetallic nitride template endohedral metallofullerene (TNT EMF), Gd3N@C-80(OH)(x)(NH2)(y), with a cage surface bearing positively charged amino groups (-NH3+) and directly compare it with a similar carboxyl and hydroxyl functionalized derivative. This new nanoparticle was characterized by X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), and infrared spectroscopy. It exhibits excellent 1H MR relaxivity. Previous studies have clearly demonstrated that the cytokine interleukin-13 (IL-13) effectively targets glioblastoma multiforme (GBM) cells, which are known to overexpress IL-13R alpha 2. We also report that this amino-coated Gd-nanoplatform, when subsequently conjugated with interleukin-13 peptide IL-13-Gd3N@C-80(OH)(x)(NH2)(y), exhibits enhanced targeting of U-251 GBM cell lines and can be effectively delivered intravenously in an orthotopic GBM mouse model.