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Transactivating transcriptional activator-mediated drug delivery

Cell-penetrating peptides (CPPs) are peptide vectors that can traverse through the plasma membrane barrier without breaching the integrity of the cell, and deliver various cargoes inside cell. The range of cargoes that can be delivered intracellularly by CPPs encompasses a broad variety of hydrophilic molecules, such as peptides, proteins, antibodies, imaging agents, DNA and even nanosized entities, including polymer-based systems, solid nanoparticles and liposomes. Multiple studies have focused on CPPs such as transactivating transcriptional activator peptide (TATp), penetratin, VP22, transportan and synthetic oligoarginines because of their high inherent potential as intracellular delivery vectors. However, the TATp remains the most popular CPP used for a variety of purposes. This review article attempts to bring together the available data on TAT-mediated intracellular uptake of a broad range of molecules and nanoparticles. It also considers potential practical applications of this approach.