State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China. Guangxi Normal University, Guilin, Guangxi 541003, China.
Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
J Med Chem. 2020 Nov 25;63(22):13695-13708. doi: 10.1021/acs.jmedchem.0c01257. Epub 2020 Nov 13.
Effective delivery of anticancer agents across the blood-brain barrier (BBB) required innovative strategies to achieve glioma regression. To resolve this problem, we proposed to develop a metal agent that target and treat glioma based on the unique property of apoferritin (AFt) nanoparticles (NPs). Thus, we synthesized a series of Au(III) 3-(4-metyl piperidine)thiosemicarbazides compounds and analyzed their structure-activity relationships, obtaining a Au agent (C6) with remarkable cytotoxicity in glioma. Moreover, we confirmed that C6 kills glioma cells by inducing lethal autophagy and apoptosis. Importantly, our results revealed that the successfully constructed apoferritin-C6 NPs (AFt-C6 NPs) can effectively cross the BBB, inhibit glioma growth, and selectively accumulate in tumors.
为了实现脑胶质瘤的消退，需要创新的策略来使抗癌药物有效地穿透血脑屏障（BBB）。为了解决这个问题，我们提出开发一种基于脱铁铁蛋白（AFt）纳米颗粒（NPs）的靶向和治疗脑胶质瘤的金属试剂。因此，我们合成了一系列的 Au(III) 3-(4-甲基哌啶)硫代半卡巴腙化合物，并分析了它们的结构-活性关系，得到了一种具有显著细胞毒性的 Au 试剂（C6）用于脑胶质瘤。此外，我们证实 C6 通过诱导致命的自噬和细胞凋亡来杀死脑胶质瘤细胞。重要的是，我们的结果表明，成功构建的脱铁铁蛋白-C6 NPs（AFt-C6 NPs）可以有效地穿透 BBB，抑制脑胶质瘤的生长，并选择性地在肿瘤中积累。
