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| Toxicity Evaluation of a FAPα-activated Targeting Anticancer Prodrug Z-GP-Dox in Zebrafish |
| MA Wei-feng1, YANG Fei-hua1, ZHAO Hai-shan2, DU Jun3, CAI Shao-hui2 |
1. School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, China;
2. College of Pharmacy Jinan University, Guangzhou 510632, China;
3. College of Pharmacy SunYat-Sen University, Guangzhou 510275, China |
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Abstract Objective: To investigate the toxicity in zebrafish of Z-GP-Dox, a novel FAPα-catalyzed activation targeted anticancer drug designed and synthesized previously. Methods: The mortality of 4-month-old zebrafish and the development of 24hpf (hours post fertilization) embryos were observed after treatment of Z-GP-Dox in different concentrations. The toxic effects of Z-GP-Dox on the zebrafish heart were evaluated with morphological and electrophysiological changes. Doxorubicin was set as a control. Results: The mortality rate of zebrafish in Dox control group showed significant does-dependent manner, while the mortality rate of the structural acylated modification prodrug Z-GP-Dox treated group was much lower. Dox induced malformations of zebrafish embryos and impaired heart function in juvenile. While at the same concentration, there was no significant difference between the Z-GP-Dox treatment group and blank control group in the heart shape and heart rate of the juvenile. When the Z-GP-Dox was hydrolysised by FAPα, its toxicity significantly increased and almost equal to the Dox. Conclusion: When compared with Dox, prodrug Z-GP-Dox toxicity was reduced significantly in zebrafish with characteristics of FAPα enzyme activated targeting release.
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Received: 22 March 2012
Published: 25 July 2012
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