Self-assembly of a metallo-peptide into a drug delivery system using a “switch on” displacement strategy†
Self-assembly of biomolecules facilitates the formation of a diverse range of nanostructures from a wide range of materials. Peptides, specifically short peptides, are very useful in this respect due to their biocompatibility, ease of synthesis, functionality and tunable bioactivity. As a result, understanding the factors that rule the morphology of the self assembled nanostructures is extremely important. Furthermore, the applications of these self-assembled nanostructures in biomedical research have intrigued researchers for a long time and recently witnessed an exponential growth. Here, we report the design and synthesis of two short (tri) peptides with similar backbones and their corresponding Cu(II) conjugates. Variation in the hydrophobicity of the central amino acid in the peptide backbone and the introduction of a metal–peptide coordination center rule the self assembly process in such a fashion that it generates various nanostructures with different morphologies. More importantly, these metallo-peptide assemblies can serve as a simple and spontaneous drug delivery system. The system delivers the drug using a fluorescence-based displacement strategy with a turn-on emission response. The naturally occurring amino acid, histidine, displaces and releases the metallo-peptide-bound drug in a controlled and immediate manner. We demonstrated the activity of this system using the efficient anticancer chemotherapy drug doxorubicin (DOX). This strategy parallelly allows the release as well as the trace of the location of the drug. Moreover, we confirmed that the system is not cytotoxic and has high cellular stability. To the best of our knowledge, this is the first report on the use of metallo-peptides as an optical-based drug displacement system.