Developing a Novel Gold(III) Agent to Treat Glioma Based on the Unique Properties of Apoferritin Nanoparticles: Inducing Lethal Autophagy and Apoptosis

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)....

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Bibliographic Details
Published in:Journal of medicinal chemistry 2020-11, Vol.63 (22), p.13695-13708
Main Authors: Zhang, Juzheng, Zhang, Zhenlei, Jiang, Ming, Li, Shanhe, Yuan, Haoliang, Sun, Hongbin, Yang, Feng, Liang, Hong
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - chemistry
Apoferritins - administration & dosage
Apoferritins - chemistry
Apoptosis - drug effects
Apoptosis - physiology
Autophagy - drug effects
Autophagy - physiology
Brain Neoplasms - drug therapy
Brain Neoplasms - pathology
Cell Line, Tumor
Female
Glioma - drug therapy
Glioma - pathology
Gold - administration & dosage
Gold - chemistry
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Nanoparticles - administration & dosage
Nanoparticles - chemistry
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.0c01257