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首页> 外文期刊>Neoplasia: an international journal for oncology research >Recombinant Interleukin-1 Receptor Antagonist Conjugated to Superparamagnetic Iron Oxide Nanoparticles for Theranostic Targeting of Experimental Glioblastoma
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Recombinant Interleukin-1 Receptor Antagonist Conjugated to Superparamagnetic Iron Oxide Nanoparticles for Theranostic Targeting of Experimental Glioblastoma

机译：重组白细胞介素-1受体拮抗剂与超顺磁性氧化铁纳米粒子缀合的实验胶质母细胞瘤的治疗靶向

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Cerebral edema commonly accompanies brain tumors and contributes to neurologic symptoms. The role of the interleukin-1 receptor antagonist conjugated to superparamagnetic iron oxide nanoparticles (SPION–IL-1Ra) was assessed to analyze its anti-edemal effect and its possible application as a negative contrast enhancing agent for magnetic resonance imaging (MRI). Rats with intracranial C6 glioma were intravenously administered at various concentrations of IL-1Ra or SPION–IL-1Ra. Brain peritumoral edema following treatment with receptor antagonist was assessed with high-field MRI. IL-1Ra administered at later stages of tumor progression significantly reduced peritumoral edema (as measured by MRI) and prolonged two-fold the life span of comorbid animals in a dose-dependent manner in comparison to control and corticosteroid-treated animals (P & .001). Synthesized SPION–IL-1Ra conjugates had the properties of negative contrast agent with high coefficients of relaxation efficiency. In vitro studies of SPION–IL-1Ra nanoparticles demonstrated high intracellular incorporation and absence of toxic influence on C6 cells and lymphocyte viability and proliferation. Retention of the nanoparticles in the tumor resulted in enhanced hypotensive T2-weighted images of glioma, proving the application of the conjugates as negative magnetic resonance contrast agents. Moreover, nanoparticles reduced the peritumoral edema confirming the therapeutic potency of synthesized conjugates. SPION–IL-1Ra nanoparticles have an anti-edemal effect when administered through a clinically relevant route in animals with glioma. The SPION–IL-1Ra could be a candidate for theranostic approach in neuro-oncology both for diagnosis of brain tumors and management of peritumoral edema.
机译：脑水肿通常伴随脑肿瘤，有助于神经系统症状。缀合与超顺磁性氧化铁纳米颗粒（Spion-IL-1RA）的白细胞介素-1受体拮抗剂的作用被评估为分析其抗Eemal效应及其作为磁共振成像（MRI）的负对比增强剂的应用。在各种浓度的IL-1RA或Spion-IL-1Ra上静脉内施用具有颅内C6胶质瘤的大鼠。用高场MRI评估接受受体拮抗剂治疗后的脑腹腔水肿。在肿瘤进展的后期施用IL-1RA显着降低了Peritumoral水肿（通过MRI测量），并且与对照和皮质类固醇处理的动物相比，延长了同血管动物的寿命，以剂量依赖性方式（P＆LT; .001）。合成的SpiOn-IL-1ra缀合物具有高造影剂的性质，具有高系数的松弛效率。 SPION-IL-1RA纳米粒子的体外研究表现出高细胞内掺入，对C6细胞和淋巴细胞活力和增殖的毒性影响。保持肿瘤中的纳米颗粒导致增强的神经瘤的低度T2加权图像，证明了缀合物的应用作为负磁共振造影剂。此外，纳米颗粒减少了突出的水肿，证实了合成缀合物的治疗效力。当通过胶质瘤动物的临床相关途径施用时，Spion-IL-1RA纳米粒子具有抗病效应。 Spion-IL-1RA可以是神经肿瘤学中的治疗方法的候选者，用于诊断脑肿瘤和Peritumoral水肿的管理。

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