Intelligent substance delivery into cells using cell-penetrating peptides

[Display omitted] Cell-penetrating peptides (CPPs) are oligopeptides that can permeate the cell membrane. The use of a CPP-mediated transport system could be an excellent method for delivering cell-impermeable substances such as proteins, antibodies, antisense oligonucleotides, siRNAs, plasmids, drugs, fluorescent compounds, and nanoparticles as covalently or noncovalently conjugated cargo into cells. Nonetheless, the mechanisms through which CPPs are internalized remain unclear. Endocytosis and direct translocation through the membrane are the generally accepted routes. Internalization via both pathways can occur simultaneously, depending on cellular conditions. However, the peculiar property of CPPs has attracted many researchers, especially in drug discovery or development, who intend to deliver impermeable substances into cells through the cell membrane. The delivery of drugs using CPPs may non-invasively solve the problem of drug penetration into cells with the added benefit of low cytotoxicity. Moreover, macromolecules can also be delivered by this transport system. In this review, I discuss the possibilities and advantages of substance delivery into cells using CPPs.