Gateways and tools for drug delivery: endocytic pathways and the cellular dynamics of cell penetrating peptides

A major goal in drug delivery is to be able to design a macromolecular entity that utilises an endocytic pathway to deliver a bioactive payload into a malfunctioning cell. However, the effectiveness of this approach may be constrained by insufficient information regarding the fate of the delivery vector within the confines of the endo-lysosomal network. Successful drug delivery through this mechanism is therefore dependent on an equal high level of understanding of the specific endocytic pathways that are inherent in the target cell and the traffic and fate of the macromolecule within endocytic organelles. Cell penetrating peptides (CPPs) are promising candidate vectors for delivering macromolecules, however, there is little consensus regarding their exact mechanism of uptake. This review highlights the numerous endocytic pathways and sorting mechanisms that may deliver CPPs to a number of cellular destinations. Our use of non-adherent leukaemia cell lines to study the cellular dynamics of CPPs HIV-TAT and octaarginine is also discussed.