Introduction The quality of an intracellular targeted imaging probe or drug depends not only on the efficient delivery across the cell membrane but also on co-localization with its intracellular targets. In recent years, cell penetrating peptides (CPPs) have been investigated for their use as delivery tools. However, several studies reported on the entrapment of CPP conjugates into endosomes af...

For almost 30 years, studies have confirmed the effectiveness of cell-penetrating peptides (CPPs) in the facilitation of the intracellular delivery of various cargo molecules, including RNA, DNA, plasmids, proteins or nanoparticles, under in vitro and in vivo conditions. The cellular uptake of CPPs occurs via energy-dependent, as well as -independent mechanisms. In this relatively new direction...

The hydrophobic plasma membrane constitutes an indispensable barrier for cells in living animals, allowing the constitutive and regulated influx of essential molecules while preventing access to the interior of cells of other macromolecules. Albeit being pivotal for the maintenance of cells, the inability to cross the plasma membrane is still one of the major obstacles to overcome in order to p...

Cell-penetrating peptides (CPPs) can traverse cellular membranes and deliver biologically active molecules into cells. In this study, we demonstrate that CPPs comprised of nona-arginine (R9) and a penetration accelerating peptide sequence (Pas) that facilitates escape from endocytic lysosomes, denoted as PR9, greatly enhance the delivery of noncovalently associated quantum dots (QDs) into human...

Cellular and nuclear delivery of biomolecules is limited by low membrane permeability. Cell-penetrating peptides (CPPs) can be covalently linked to cargos to improve cellular internalization. Our work indicates that arginine-rich CPPs are also able to interact with a variety of cargos, including DNA, RNA, proteins and nanomaterials, in a noncovalent manner and subsequently effect their delivery...

We describe a strategy for rendering peptides resistant to proteolysis by formulating them as high-density brush polymers. The utility of this approach is demonstrated by polymerizing well-established cell-penetrating peptides (CPPs) and showing that the resulting polymers are not only resistant to proteolysis but also maintain their ability to enter cells. The scope of this design concept is e...

Maurocalcine is the first demonstrated example of an animal toxin peptide with efficient cell penetration properties. Although it is a highly competitive cell-penetrating peptide (CPP), its relatively large size of 33 amino acids and the presence of three internal disulfide bridges may hamper its development for in vitro and in vivo applications. Here, we demonstrate that several efficient CPPs...

BACKGROUND Cell-penetrating peptides (CPPs) have been widely used as carriers to transport different molecules into living cells, whereas messenger RNAs (mRNAs) have been utilized as target molecules for the prevention and treatment of various diseases. However, the instability of CPPs and mRNAs has limited their application. Bacteriophage PP7 virus-like particles (VLPs) may protect peptides an...

Cationic CPPs (cell-penetrating peptides) have been used largely for intracellular delivery of low-molecular-mass drugs, biomolecules and particles. Most cationic CPPs bind to cell-associated glycosaminoglycans and are internalized by endocytosis, although the detailed mechanisms involved remain controversial. Sequestration and degradation in endocytic vesicles severely limits the efficiency of...

Cell-penetrating peptides can translocate across the plasma membrane of living cells and thus are potentially useful agents in drug delivery applications. Disulfide-rich cyclic peptides also have promise in drug design because of their exceptional stability, but to date only one cyclic peptide has been reported to penetrate cells, the Momordica cochinchinensis trypsin inhibitor II (MCoTI-II). M...