Furin substrate as a novel cell-penetrating peptide: combining a delivery vector and an inducer of cargo release.

We have developed a new cell-penetrating peptide (CPP) using a repeated protease (furin) substrate. This CPP can not only deliver cargo into cells but can also be cleaved by furin in cells and release the cargo. Cell-impermeable antitumor pro-apoptotic peptide KLAKLAKKLAKLAK (KLA) and chemotherapy drug chlorambucil were chosen to be delivered by the CPP into live cancer cells and their cytotoxicity was greatly enhanced for in vivo cancer treatment.