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.
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Authors | Jie Li, Yi Kuang, Junfeng Shi, Jie Zhou, Jamie E Medina, Rong Zhou, Dan Yuan, Cuihong Yang, Huaimin Wang, Zhimou Yang, Jianfeng Liu, Daniela M Dinulescu, Bing Xu |
Journal | Angewandte Chemie (International ed. in English)
(Angew Chem Int Ed Engl)
Vol. 54
Issue 45
Pg. 13307-11
(Nov 02 2015)
ISSN: 1521-3773 [Electronic] Germany |
PMID | 26365295
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Copyright | © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Chemical References |
- Antineoplastic Agents
- Peptides
- Carboxylesterase
- Cisplatin
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Topics |
- Antineoplastic Agents
(chemistry, pharmacology)
- Carboxylesterase
(metabolism)
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Cisplatin
(chemistry, pharmacology)
- Dose-Response Relationship, Drug
- Drug Resistance, Neoplasm
(drug effects)
- Female
- Humans
- Molecular Structure
- Ovarian Neoplasms
(drug therapy, pathology)
- Peptides
(chemistry, metabolism)
- Structure-Activity Relationship
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