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Novel Conjugation of Tumor-Necrosis-Factor-Related Apoptosis-Inducing Ligand (TRAIL) with Monomethyl Auristatin E for Efficient Antitumor Drug Delivery

Authors

  • Li-Qiang Pan,

    1. Department of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
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  • Hai-Bin Wang,

    1. Department of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
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  • Zhang-Ming Xie,

    1. Department of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
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  • Zhao-Hui Li,

    1. Department of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
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  • Xiao-Jing Tang,

    1. Department of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
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  • Ying-Chun Xu,

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

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

    1. Department of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
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  • Shu-Qing Chen

    Corresponding author
    1. Department of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
    • Department of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
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  • Dedicated to the 100th anniversary of the College of Pharmaceutical Sciences, Zhejiang University

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.

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