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Modulowanie właściwości peptydów penetrujących do komórek

Lipiński W., Kolesińska B.

Wiadomości Chemiczne

2017

[Z] 71, 9-10

695--726

Cell penetrating peptides (CPPs) are short peptides able to efficiently cross cellular membrane. The group includes great diversity of sequences and besides capability to enter various types of cells, their characteristic feature is lack of toxicity. CPPs can be divided according to their origin (natural and synthetic) or according to their physicochemical properties responsible for the cellpenetrating ability (cationic, amphipathic and hydrophobic). Properties of CPPs are closely related to their mechanism of internalisation. Endocytic pathway is probably the dominating mechanism for majority of CPPs, but less common energyindependent internalisation (occurring via inverted micelle, carpet-like, barrel stave pore or toroidal pore model may also play a relevant part in the uptake across membranes. CPPs have been applied in transporting various compounds. They are very effective in delivering small molecules (fluorophores, drugs, peptides), macromolecules (proteins, nucleic acids) and even nanoparticles (metal nanoparticles, liposomes). Conjunction of CPP and cargo can be achieved either covalently (peptide bond, sulphide bridge etc.) or noncovalently (electrostatic or hydrophobic interaction, hydrogen bonding). Ability to unspecific enter almost any kind of cell and tissue becomes a great problem in the case of in vivo applications. Another disadvantage of CPPs is their low plasma stability. Many strategies have been suggested to overcome these issues. Selectivity can be improved by attaching targeting ligands (e.g. short peptides, antibodies, proteins, folic acid or hyaluronic acid) or by incorporating CPPs into macromolecular drug carriers, which exploit the so called enhanced permeability and retention (EPR) effect. The most recent and most sophisticated way of improving CPPs’ stability and selectivity is the synthesis of activatable cell penetrating peptides (ACPPs). The deactivating moiety may consist of anionic sequence, polymer chain or smaller protecting groups. The deactivating parts are connected to the delivery system via linker that can be cleaved under conditions characteristic for the site of action. ACPPs may be activated by enzymes, pH and oxidative potential change, temperature or radiation. CPPs may find application in tumour therapy, diagnostics and the combination of both – theranostics. Despite many successful studies in delivering drugs and tags in vivo and in vitro, CPPs have passed only few clinical trials (some are being run currently). It is sure that this research area will develop in next years