A very poor cell permeability and low bioavailability is a hallmark of many prospective therapeutic and diagnostic agents. Cell-penetrating peptides or CPPs, also known as protein transduction domains have the ability to translocate through cell membranes. Cell-penetrating peptides are short peptides that can facilitate cellular uptake of various molecular cargos ranging from nanosized particles to small chemical molecules and large fragments of DNA or peptides and proteins. In recent years they have received increased attention since they are believed to be promising tools to help overcome drug delivery problems. Cell penetrating peptides (CPPs) have been used to deliver drugs, imaging agents, and other therapeutic biomolecules across the cell membrane into the cytoplasm. Although the mechanism of their intracellular translocation is not clearly established they have a unique amino acid composition which gives them a net positive charge that seems to play a key role in this process. Typically cell penetrating peptides have an amino acid composition that either contains a high relative abundance of positively charged amino acids such as lysine or arginine or has sequences that contain an alternating pattern of polar or charged amino acids and non-polar or hydrophobic amino acids. These structural types are often referred to as polycationic or amphipathic. Over the years researchers have performed several studies in which they hypothesized that internalization occurs via endocytosis, a direct transport through the cell membrane or both. Several naturally occurring and synthetic cell penetrating peptides have been investigated for their ability to deliver various cargos into cells such as nucleic acids, proteins, quantum dots, contrast agents and small organic molecules. In all of these studies it was shown that CPPs exhibited minimal toxicity in biological systems, suggesting their potential as unique drug delivery vehicles. In addition, these peptides can be used for many more applications for example to deliver oligonucleotides for siRNA and antisense strategies, deliver decoy DNA, therapeutic proteins or contrast agents, to name a few. 10/13
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