Issue 20, 2011

Switching of self-assembly in a peptide nanostructure with a specific enzyme

Abstract

Peptide self-assembly has been shown to be a useful tool for the preparation of bioactive nanostructures, and recent work has demonstrated their potential as therapies for regenerative medicine. In principle, one route to make these nanostructures more biomimetic would be to incorporate in their molecular design the capacity for biological sensing. We report here on the use of a reversible enzymatic trigger to control the assembly and disassembly of peptide amphiphile (PA) nanostructures. The PA used in these studies contained a consensus substrate sequence specific to protein kinase A (PKA), a biological enzyme important for intracellular signaling that has also been shown to be an extracellular cancer biomarker. Upon treatment with PKA, this PA molecule becomes phosphorylated causing the high aspect-ratio filamentous PA nanostructures to disassemble. Treatment with an enzyme to cleave the phosphate group results in reformation of the filamentous nanostructures. We also show that disassembly in the presence of PKA allows the enzyme-triggered release of an encapsulated cancer drug. In addition, these drug-loaded nanostructures were found to induce preferential cytotoxicity in a cancer cell line that is known to secrete high levels of PKA. This ability to control nanostructure through an enzymatic switch could allow for the preparation of highly sophisticated and biomimetic materials that incorporate a biological sensing capability to enable therapeutic specificity.

Graphical abstract: Switching of self-assembly in a peptide nanostructure with a specific enzyme

Supplementary files

Article information

Article type
Paper
Submitted
06 Apr 2011
Accepted
31 May 2011
First published
14 Jul 2011

Soft Matter, 2011,7, 9665-9672

Switching of self-assembly in a peptide nanostructure with a specific enzyme

M. J. Webber, C. J. Newcomb, R. Bitton and S. I. Stupp, Soft Matter, 2011, 7, 9665 DOI: 10.1039/C1SM05610G

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