Cell-permeable peptide-based delivery vehicles useful for subcellular targeting and beyond

Abstract

Personal medicine aims to provide tailor-made diagnostics and treatments and has been emerged as a promising but challenging strategy during the last years. This includes the active delivery and localization of a therapeutic compound to a targeted site of action within a cell. An example being targeting the interference of a distinct protein-protein interaction (PPI) within the cell nucleus, mitochondria or other subcellular location. Therefore, not only the cell membrane has to be overcome but also the final intracellular destination has to be reached. One approach which fulfills both requirements is to use short peptide sequences that are able to translocate into cells as targeting and delivery vehicles. In fact, recent progress in this field demonstrates how these tools can modulate the pharmacological parameters of a drug without compromising its biological activity. Beside classical targets that are addressed by various small molecule drugs such as receptors, enzymes, or ion channels, PPIs have received increasing attention as potential therapeutic targets. Within this review, we will provide a recent update on cell-permeable peptides targeting subcellular destinations. We include chimeric peptide probes that combine cell-penetrating peptides (CPPs) and a targeting sequence, as well peptides having intrinsic cell-permeability and which are often used to target PPIs.

Keywords: Cell-penetrating peptide; Drug delivery; Organelles; Peptide–drug conjugates; Protein–protein interactions; Subcellular targeting.