Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 53, Issue 31, Pages 8104-8107Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201402216
Keywords
cancer; hydrogel; inhibition; nanofibrils; pericellular space
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Funding
- NIH [R01A142746]
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Fibrils formed by proteins are vital components for cells. However, selective formation of xenogenous nanofibrils of small molecules on mammalian cells has yet to be observed. Here we report an unexpected observation of hydrogel/nanonets of a small D-peptide derivative in pericellular space. Surface and secretory phosphatases dephosphorylate a precursor of a hydrogelator to trigger the self-assembly of the hydrogelator and to result in pericellular hydrogel/nanonets selectively around the cancer cells that overexpress phosphatases. Cell-based assays confirm that the pericellular hydrogel/nanonets block cellular mass exchange to induce apoptosis of cancer cells, including multidrug-resistance (MDR) cancer cells, MES-SA/Dx5. Pericellular hydrogel/nanonets of small molecules to exhibit distinct functions illustrates a fundamentally new way to engineer molecular assemblies spatiotemporally in cellular microenvironment for inhibiting cancer cell growth and even metastasis.
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