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Glioma-sensitive delivery of Angiopep-2 conjugated iron gold alloy nanoparticles ensuring simultaneous tumor imaging and hyperthermia mediated cancer theranostics
Applied Materials Today ( IF 8.3 ) Pub Date : 2019-11-26 , DOI: 10.1016/j.apmt.2019.100510
Sanford P.C. Hsu , Udesh Dhawan , Yuan-Yun Tseng , Ching-Po Lin , Ching-Yu Kuo , Li-Fang Wang , Ren-Jei Chung

Gliomas display a poor disease prognosis causing death within 15 months after diagnosis. Chemotherapy has offered some hope to target this, however, it is majorly ineffective due to the low therapeutic window, poor efficacy and high cytotoxicity. To overcome these challenges, we conjugated Angiopep-2, a cell penetrating peptide (CPP) to Iron Gold (Fe-Au) alloy nanoparticles and investigated the ability of Ang-Fe-Au Nps conjugate to limit glioma growth via magnetic field induced hyperthermia. Our results show that 6.44 nm sized conjugated Fe-Au Nps were superparamagnetic, enhanced negative Glioma image contrast and displayed a 12 °C temperature elevation when magnetically stimulated, indicating applications in medical imaging and hyperthermia-based therapy. Angiopep-2 conjugation resulted in 1.5-fold higher ingestion by C6 glioma cells than L929 fibroblasts, indicating specific glioma targeting and resulting in 90 % decrement in cell viability due to magnetic field induced hyperthermia. Immunohistochemical analysis showed an enhanced coagulative necrosis, glial fibrillary acidic protein (GFAP) expression and decreased Ki67 labelling index in rat treated with Ang-Fe-Au Nps which translated to a 5-fold decrement in tumor volume, consequently resulting in an increased survival time by 7 days. The dual application of this platform opens new doors towards cancer theranostics with minimal invasiveness.



中文翻译:

胶质瘤敏感的Angiopep-2共轭铁金合金纳米颗粒的递送,确保同时进行肿瘤成像和热疗介导的癌症治疗学

神经胶质瘤显示出不良的疾病预后,导致诊断后15个月内死亡。化学疗法提供了一些希望以此为目标,但是,由于治疗窗口低,疗效差和细胞毒性高,它主要无效。为了克服这些挑战,我们将细胞穿透肽(CPP)Angiopep-2与铁金(Fe-Au)合金纳米粒子结合,并研究了Ang-Fe-Au Nps结合物通过磁场诱导的高温限制神经胶质瘤生长的能力。我们的结果表明,6.44 nm大小的共轭Fe-Au Nps具有超顺磁性,可增强负胶质瘤图像对比度,并在磁刺激时显示12°C的温度升高,表明其在医学成像和基于热疗的疗法中的应用。Angiopep-2缀合导致1。C6胶质瘤细胞的摄取比L929成纤维细胞高5倍,这表明针对特定胶质瘤的靶向作用由于磁场诱导的高热而导致细胞活力降低90%。免疫组织化学分析显示,用Ang-Fe-Au Nps治疗的大鼠中凝血坏死增强,神经胶质纤维酸性蛋白(GFAP)表达降低和Ki67标记指数降低,这意味着肿瘤体积减少了5倍,从而导致存活时间增加到7天。该平台的双重应用为癌症治疗学带来了最小限度的侵害,为癌症治疗学开辟了新的大门。Ang-Fe-Au Nps治疗的大鼠中胶质纤维酸性蛋白(GFAP)的表达和Ki67标记指数的降低,转化为肿瘤体积减少了5倍,因此导致生存时间增加了7天。该平台的双重应用为癌症治疗学带来了最小限度的侵害,为癌症治疗学开辟了新的大门。Ang-Fe-Au Nps治疗的大鼠中胶质纤维酸性蛋白(GFAP)的表达和Ki67标记指数的降低,转化为肿瘤体积减少了5倍,因此导致生存时间增加了7天。该平台的双重应用为癌症治疗学带来了最小的侵入性,为癌症治疗学开辟了新的大门。

更新日期:2019-11-26
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