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“Golgi-customized Trojan horse” nanodiamonds impair GLUT1 plasma membrane localization and inhibit tumor glycolysis
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2024-06-05 , DOI: 10.1016/j.jconrel.2024.05.025
Bei Kang 1 , Haobo Wang 1 , Huaqing Jing 1 , Yunsheng Dou 1 , Sona Krizkova 2 , Zbynek Heger 2 , Vojtech Adam 2 , Nan Li 1
Affiliation  

Nutrient or energy deprivation, especially glucose restriction, is a promising anticancer therapeutic approach. However, establishing a precise and potent deprivation strategy remains a formidable task. The Golgi morphology is crucial in maintaining the function of transport proteins (such as GLUT1) driving glycolysis. Thus, in this study, we present a “Golgi-customized Trojan horse” based on tellurium loaded with apigenin (4′,5,7-trihydroxyflavone) and human serum albumin, which was able to induce GLUT1 plasma membrane localization disturbance Golgi dispersal leading to the inhibition of tumor glycolysis. Diamond-shaped delivery system can efficiently penetrate into cells as a gift like Trojan horse, which decomposes into tellurite induced by intrinsically high HO and GSH levels. Consequently, tellurite acts as released warriors causing up to 3.8-fold increase in Golgi apparatus area due to the down-regulation of GOLPH3. Further, this affects GLUT1 membrane localization and glucose transport disturbance. Simultaneously, apigenin hinders ongoing glycolysis and causes significant decrease in ATP level. Collectively, our “Golgi-customized Trojan horse” demonstrates a potent antitumor activity because of its capability to deprive energy resources of cancer cells. This study not only expands the applications of tellurium-based nanomaterials in the biomedicine but also provides insights into glycolysis restriction for anticancer therapy.

中文翻译:


“高尔基定制特洛伊木马”纳米金刚石损害GLUT1质膜定位并抑制肿瘤糖酵解



营养或能量剥夺,尤其是葡萄糖限制,是一种有前途的抗癌治疗方法。然而,建立精确而有效的剥夺策略仍然是一项艰巨的任务。高尔基体形态对于维持驱动糖酵解的转运蛋白(例如 GLUT1)的功能至关重要。因此,在本研究中,我们提出了一种基于载有芹菜素(4',5,7-三羟基黄酮)和人血清白蛋白的碲的“高尔基定制特洛伊木马”,它能够诱导 GLUT1 质膜定位紊乱,导致高尔基体扩散从而抑制肿瘤糖酵解。菱形输送系统可以像特洛伊木马一样有效地渗透到细胞中,在本质上高水平的 H2O 和 GSH 诱导下分解成亚碲酸盐。因此,亚碲酸盐充当释放的战士,由于 GOLPH3 的下调,导致高尔基体面积增加高达 3.8 倍。此外,这还会影响 GLUT1 膜定位和葡萄糖转运干扰。同时,芹菜素会阻碍正在进行的糖酵解并导致 ATP 水平显着下降。总的来说,我们的“高尔基定制特洛伊木马”由于能够剥夺癌细胞的能量资源而表现出强大的抗肿瘤活性。这项研究不仅扩大了碲基纳米材料在生物医学中的应用,而且还为抗癌治疗中的糖酵解限制提供了见解。
更新日期:2024-06-05
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