Developing a Novel Gold(III) Agent to Treat Glioma Based on the Unique Properties of Apoferritin Nanoparticles: Inducing Lethal Autophagy and Apoptosis
Juzheng Zhang, Zhenlei Zhang, Ming Jiang, Shanhe Li, Haoliang Yuan, Hongbin Sun, Feng Yang, Hong Liang
Abstract
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.