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Enzyme-Instructed Intracellular Molecular Self-Assembly to Boost Activity of Cisplatin against Drug-Resistant Ovarian Cancer Cells.


ABSTRACT: 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.

SUBMITTER: Li J 

PROVIDER: S-EPMC4681442 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Enzyme-Instructed Intracellular Molecular Self-Assembly to Boost Activity of Cisplatin against Drug-Resistant Ovarian Cancer Cells.

Li Jie J   Kuang Yi Y   Shi Junfeng J   Zhou Jie J   Medina Jamie E JE   Zhou Rong R   Yuan Dan D   Yang Cuihong C   Wang Huaimin H   Yang Zhimou Z   Liu Jianfeng J   Dinulescu Daniela M DM   Xu Bing B  

Angewandte Chemie (International ed. in English) 20150914 45


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-in  ...[more]

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