Mechanistic aspects of CPP-mediated intracellular drug delivery: relevance of CPP self-assembly.
In recent years, cell-penetrating peptides have proven to be an efficient intracellular delivery system. The mechanism for CPP internalisation, which first involves interaction with the extracellular matrix, is followed in most cases by endocytosis and finally, depending on the type of endocytosis, an intracellular fate is reached. Delivery of cargo attached to a CPP requires endosomal release, for which different methods have recently been proposed. Positively charged amino acids, hydrophobicity and/or amphipathicity are common to CPPs. Moreover, some CPPs can self-assemble. Herein is discussed the role of self assembly in the cellular uptake of CPPs. Sweet Arrow Peptide (SAP) CPP has been shown to aggregate by CD and TEM (freeze-fixation/freeze-drying), although the internalised species have yet to be identified as either the monomer or an aggregate.
Pujals
Sílvia
S
Institut de Recerca Biomèdica de Barcelona, Parc Científic de Barcelona, Josep Samitier 1-5, E-08028 Barcelona, Spain.
Fernández-Carneado
Jimena
J
López-Iglesias
Carmen
C
Kogan
Marcelo J
MJ
Giralt
Ernest
E
D000595:Amino Acid Sequence; D000818:Animals; D004337:Drug Carriers / Q000378:metabolism*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D021381:Protein Transport
D004337:Drug Carriers; D010455:Peptides; C512362:sweet arrow peptide