07-Nov-2015 05:31

Elucidating the mechanism of cellular uptake

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Recently, much attention has been given to the problem of drug delivery through the cell-membrane in order to treat and manage several diseases.

CPPs are rich in basic amino acids such as arginine and lysine and are able to translocate over membranes and gain access to the cell interior.The cell membrane is the structure that protects living cells from the surrounding environment, only allowing the movement of compounds generally with small molecular size across this barrier into the cell.Some drugs are large hydrophilic molecules showing major limitations for their penetration through the cell membrane.A group of short peptides have been discovered that serve as delivery vectors for large molecules.They may have been called by different names such as protein translocation domain, membrane translocating sequence, Trojan peptide, or most commonly, cell-penetrating peptide (CPP).They can deliver large-cargo molecules, such as oligonucleotides, into cells.

Endocytosis and direct penetration have been suggested as the two major uptake mechanisms, a subject still under debate.

Unresolved questions include the detailed molecular uptake mechanism(s), reasons for cell toxicity, and the delivery efficiency of CPPs for different cargoes.

Here, we give a review focused on uptake mechanisms used by CPPs for membrane translocation and certain experimental factors that affect the mechanism(s).

Generally, CPPs are defined as short, water-soluble and partly hydrophobic, and/or polybasic peptides (at most 30–35 amino acids residues) with a net positive charge at physiological p H [1].

The main feature of CPPs is that they are able to penetrate the cell membrane at low micromolar concentrations in vivo and in vitro without using any chiral receptors and without causing significant membrane damage.

Furthermore, and even more importantly, these peptides are capable of internalizing electrostatically or covalently bound biologically active cargoes such as drugs with high efficiency and low toxicity [1, 2].

Profile for elucidating the mechanism of cellular uptake:

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