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Enzyme‐Instructed Intracellular Molecular Self‐Assembly to Boost Activity of Cisplatin against Drug‐Resistant Ovarian Cancer Cells
Author(s) -
Li Jie,
Kuang Yi,
Shi Junfeng,
Zhou Jie,
Medina Jamie E.,
Zhou Rong,
Yuan Dan,
Yang Cuihong,
Wang Huaimin,
Yang Zhimou,
Liu Jianfeng,
Dinulescu Daniela M.,
Xu Bing
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201507157
Subject(s) - cisplatin , ovarian cancer , intracellular , drug , chemistry , drug resistance , carboxylesterase , enzyme , cancer cell , pharmacology , cancer research , cancer , biochemistry , biology , chemotherapy , medicine , genetics
Anticancer drug resistance demands innovative approaches that boost the activity of drugs against drug‐resistant cancers without increasing the systemic toxicity. Here we show the use of enzyme‐instructed self‐assembly (EISA) to generate intracellular supramolecular assemblies that drastically boost the activity of cisplatin against drug‐resistant ovarian cancer cells. We design and synthesize small peptide precursors as the substrates of carboxylesterase (CES). CES cleaves the ester bond pre‐installed on the precursors to form the peptides that self‐assemble in water to form nanofibers. At the optimal concentrations, the precursors themselves are innocuous to cells, but they double or triple the activity of cisplatin against the drug‐resistant ovarian cancer cells. This work illustrates a simple, yet fundamental, new way to introduce non‐cytotoxic components into combination therapies with cisplatin without increasing the systemic burden or side effects.