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JOURNAL ARTICLE
REVIEW
Cell Penetrating Peptides: A Promising Tool for the Cellular Uptake of Macromolecular Drugs.
The lipid bilayer of the plasma membrane is a selective impermeable barrier for the internalization of most macromolecules. Cell penetrating peptides (CPPs) could cross the plasma membrane barrier to deliver various molecules into cells and are considered as a promising tool to deliver macromolecular drugs. However, the exact cellular uptake mechanisms of CPPs are still ambiguous. It was reported that the exact cellular uptake pathway was determined by numerous factors such as the amino acid sequences (hydrophobicity and net charge), extracellular CPP concentration, cargoes' properties, cell type and the temperature. No matter what kind of mechanisms, the electrostatic interaction between the positive charged amino acids and the membrane with negatively charged glycosaminoglycans (GAGs), especially heparan sulphate proteoglycans (HSPGs), was supposed to be the first crucial step for CPPs uptake. The first recognition triggers cytoskeletal remodeling via activating Rho/Rac GTPases and kinase C, followed by the cell surface microdomains changing, ligand binding and cellular uptake. This review briefly discusses the classification, structure-activity relationships, cellular uptake mechanisms and biomedical applications of CPPs.
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