Enzymatic activation of a peptide functionalised gold nanoparticle system for prodrug delivery.

Abstract

Traditional chemotherapeutic drugs are often restricted by severe side effects and a lack of specificity. An approach aimed at improving the selectivity of cancer drugs includes the use of prodrugs that can be selectively activated in tumour tissue (tumour-activated prodrugs). Peptide prodrugs cleavable by proteases in the tumour environment have been widely explored to improve the therapeutic index of cytotoxic drugs. In this study we demonstrate that the cell surface proteases over expressed in tumour cells are capable of cleaving the peptide CKAFKRK attached to gold nanoparticles (GNPs). This proteolic cleavage exposes the potential cytotoxic “agent” to the tumour cell. As these proteases are not over expressed in healthy cells, the prodrug will take much longer to be activated. A simple system is developed in this study as a proof of concept by replacing the cytotoxic agent with a fluorophore. An enhanced fluorescence emission is expected on exposure of the peptide functionalised GNP to the tumour cells, whereas a constant level of emission is anticipated on exposure to the healthy cell line.