A camptothecin-based, albumin-binding prodrug enhances efficacy and safety in vivo
文献类型：期刊论文
| 作者 | Cheng, Zhiyang1; Huang, Ying1; Shen, Qianqian2; Zhao, Yangrong2; Wang, Lei1; Yu, Jiahui1; Lu, Wei1 |
| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2021-12-15 |
| 卷号 | 226页码:11 |
| ISSN号 | 0223-5234 |
| 关键词 | Cancer beta-glucuronidase Bioconjugation Albumin Camptothecin |
| DOI | 10.1016/j.ejmech.2021.113851 |
| 通讯作者 | Wang, Lei(lwang@chem.ecnu.edu.cn) ; Lu, Wei(wlu@chem.ecnu.edu.cn) |
| 英文摘要 | The albumin-based drug delivery system is an effective drug delivery strategy for traditional chemotherapeutic drugs that can improve their antitumour efficacies and reduce systemic toxicities. The camptothecin derivative CPTS0001 has excellent antitumour activity in vitro, but it shows toxicity and side effects in vivo. In this study, we report the synthesis and biological evaluation of the beta-glucuronidase-reactive albumin-binding prodrug Mal-glu-CPTS0001 based on quaternary ammonium. After intravenous administration, the compound covalently binds to plasma albumin through Michael addition, enabling it to accumulate in tumours, where tumour-associated beta-glucuronidase triggers the selective release of CPTS0001. This prodrug significantly reduced the toxicity of the parent drug, and the maximum tolerated dose was increased by 2.5 times. At the same time, this prodrug enhanced the selectivity in vivo and improved the preferential accumulation of prodrug in tumours. Notably, this prodrug exhibited excellent in vivo antitumour effects in a murine breast cancer xenograft model without visible pathological toxicity. (C) 2021 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | DRUG-DELIVERY ; BIOLOGICAL EVALUATION ; DERIVATIVES ; DOXORUBICIN ; NANOPARTICLES ; CONJUGATE ; RELEASE ; DESIGN ; VITRO |
| 资助项目 | Fundamental Research Funds for the Central Universities ; National Natural Science Foundation of China[22077034] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| WOS记录号 | WOS:000703119000033 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/297452]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Wang, Lei; Lu, Wei |
| 作者单位 | 1.East China Normal Univ, Sch Chem & Mol Engn, 3663 North Zhongshan Rd, Shanghai 200062, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cheng, Zhiyang,Huang, Ying,Shen, Qianqian,et al. A camptothecin-based, albumin-binding prodrug enhances efficacy and safety in vivo[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2021,226:11. |
| APA | Cheng, Zhiyang.,Huang, Ying.,Shen, Qianqian.,Zhao, Yangrong.,Wang, Lei.,...&Lu, Wei.(2021).A camptothecin-based, albumin-binding prodrug enhances efficacy and safety in vivo.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,226,11. |
| MLA | Cheng, Zhiyang,et al."A camptothecin-based, albumin-binding prodrug enhances efficacy and safety in vivo".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 226(2021):11. |
入库方式： OAI收割
来源：上海药物研究所
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