State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, P. R. China.
Biomater Sci. 2019 Feb 26;7(3):1052-1063. doi: 10.1039/c8bm01414k.
The incidence of papillary thyroid cancer has rapidly increased in the past decade because of the progress in modern diagnostic technology. Novel therapeutic strategies for papillary thyroid cancer (which has low malignancy) based on organelle-targeted nanomaterials are greatly welcome in order to avoid over-treatment by conventional surgery. Herein, we demonstrate the mitochondria-targeted and exocytosis inhibition strategy of polydopamine (PDA)-coated inorganic nanoparticles (NPs) for enhanced papillary thyroid cancer therapy. PDA-coated gold-silver alloy NPs (Au-Ag@PDA NPs) were employed as the model of composite NPs. TPC-1 cells were chosen as the model of human papillary thyroid cancer cells. To better understand the effect of composite NPs on papillary thyroid cancer cells, the intracellular fate and corresponding cellular responses of Au-Ag@PDA NPs in TPC-1 cells were studied. The results indicate that Au-Ag@PDA NPs are internalized through a caveolae-mediated and macropinocytosis pathway and they are difficult to excrete by the TPC-1 cells. Au-Ag@PDA NPs mainly accumulate in mitochondria, resulting in the mitochondrial dysfunction and the decreased expression of dihydroorotate dehydrogenase. This leads to up-regulation of the p53 levels and therefore the S-phase cell cycle arrest and cell proliferation inhibition. In addition, despite cancer cells being able to survive by an autophagy-mediated pathway to escape apoptosis or necrosis, targeting mitochondria by Au-Ag@PDA NPs enables the destructive thermal ablation of TPC-1 cells by combination with photothermal therapy.
在过去的十年中，由于现代诊断技术的进步，甲状腺乳头状癌的发病率迅速上升。为了避免常规手术的过度治疗，人们非常欢迎基于细胞器靶向纳米材料的新型甲状腺乳头状癌（恶性程度低）治疗策略。在此，我们展示了基于聚多巴胺（PDA）涂层的无机纳米粒子（NPs）的靶向线粒体和抑制细胞外排的策略，用于增强甲状腺乳头状癌的治疗效果。PDA 涂层的金-银合金 NPs（Au-Ag@PDA NPs）被用作复合 NPs 的模型。TPC-1 细胞被选为人类甲状腺乳头状癌细胞的模型。为了更好地理解复合 NPs 对甲状腺乳头状癌细胞的影响，研究了 Au-Ag@PDA NPs 在 TPC-1 细胞中的细胞内命运和相应的细胞反应。结果表明，Au-Ag@PDA NPs 通过网格蛋白介导的和巨胞饮作用途径被内化，并且它们很难被 TPC-1 细胞排出。Au-Ag@PDA NPs 主要积聚在线粒体中，导致线粒体功能障碍和二氢乳清酸脱氢酶表达降低。这导致 p53 水平上调，从而导致 S 期细胞周期停滞和细胞增殖抑制。此外，尽管癌细胞可以通过自噬介导的途径存活，以逃避细胞凋亡或坏死，但通过 Au-Ag@PDA NPs 靶向线粒体，可以与光热疗法相结合，对 TPC-1 细胞进行破坏性的热消融。
