Pericellular Hydrogel/Nanonets Inhibit Cancer Cells

• Published in: Angewandte Chemie International Edition Vol. 53; no. 31; pp. 8104 - 8107
• Main Authors: Kuang, Yi, Shi, Junfeng, Li, Jie, Yuan, Dan, Alberti, Kyle A., Xu, Qiaobing, Xu, Bing
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 28.07.2014; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Apoptosis; Cancer; Cellular; Chemistry; Chemistry, Multidisciplinary; Derivatives; Drug resistance; Formations; HeLa Cells; Humans; hydrogel; Hydrogels; inhibition; Medical research; Microscopy, Electron, Scanning; nanofibrils; Nanostructure; Neoplasms - pathology; Peptides; pericellular space; Phosphatase; Physical Sciences; Rodents; Science & Technology; Self assembly; VANCOMYCIN; CONFER; hydrogel; pericellular space; ALKALINE-PHOSPHATASE; inhibition; cancer; CANDIDATE; nanofibrils; SUPRAMOLECULAR HYDROGELS; ENZYMATIC FORMATION
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.201402216

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. A small D‐peptide derivative is reported to form fibrils and nanonets in the pericellular space. The pericellular nanonets encapsulate cancer cells, which not only prohibits cell adhesion but also selectively induces cancer cell apoptosis. This is the first example of synthetic peptides to achieve biological function through formation of nanonets.