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新型肿瘤坏死因子相关凋亡诱导配体（TRAIL）与单甲基奥瑞他汀 E 的缀合用于高效抗肿瘤药物传递。

Novel conjugation of tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) with monomethyl auristatin E for efficient antitumor drug delivery.

机构信息

Department of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.

出版信息

Adv Mater. 2013 Sep 14;25(34):4718-22. doi: 10.1002/adma.201301385. Epub 2013 Jul 12.

DOI:10.1002/adma.201301385
PMID:23847045
Abstract

Monomethyl auristatin E (MMAE) is conjugated with TNF-related apoptosis-inducing ligand (TRAIL) via a linker that is stable in extracellular fluid, while it is cleaved by cathepsin once the conjugate has entered a tumor cell, thus activating the antimitotic mechanism of MMAE. The TRAIL-MMAE conjugate is a conceptually viable therapeutic strategy with improved in vitro antitumor activity, cell circle arrest and specific accumulation in tumor to treat TRAIL-resistant tumors.

摘要

单甲基澳瑞他汀 E（MMAE）通过一个在细胞外液中稳定的连接子与 TNF 相关凋亡诱导配体（TRAIL）偶联，一旦偶联物进入肿瘤细胞，它就会被组织蛋白酶裂解，从而激活 MMAE 的抗有丝分裂机制。TRAIL-MMAE 偶联物是一种概念上可行的治疗策略，具有增强的体外抗肿瘤活性、细胞周期停滞和在肿瘤中的特异性积累，可用于治疗 TRAIL 耐药肿瘤。

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