Department of Chemical and Biomolecular Engineering

The Johns Hopkins University

3400 N. Charles Street, Baltimore, MD 21218, USA.

 

The reversible nature of supramolecular polymers provides unique properties that expand the functional space of classical covalent polymers. One particular type of supramolecular polymers consists of shape-persistent nanostructures that can be constructed by self-assembly of small molecular building units possessing strong, associative interactions. Peptides offer great molecular attributes as an effective building block to construct supramolecular polymers for biomedical applications that incorporate explicit bioactivities into well-defined structural features at the nanoscale. In this presentation, I will cover two aspects of our recent research effort in the design and creation of peptide-based supramolecular assemblies for tumor microenvironment mimicking and for cancer diagnosis. In the first part, I will present our strategies of using beta-sheet forming peptides to create supramolecular filaments that could further entangle into a 3D network under appropriate conditions. Our goal is to be able to achieve independent control over four important parameters that are critical for cancer migration: mechanical properties, mesh size, surface chemistry, and degradability by enzymes expressed by cancer cells. The second part of the presentation is focused on the design of supramolecular nanoprobes for cancer diagnosis. This strategy employs a molecular beacon approach to take advantage of the specific cleavage of certain peptide sequences by enzymes that are closely associated with cancer progression. Precisely probing the activities and expression level of these enzymes provides opportunities for early stage cancer diagnosis. Our results have shown that our designed supramolecular nanoprobe can be used as effective sensors for visualization and quantification of a lysosomal enzyme, cathepsin B.