CPP

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Introductions

Cell-penetrating peptides (CPPs) are a class of short peptides that can cross cell membranes or tissue barriers and carry proteins, RNA, DNA and other biomolecules into cells through endocytosis and direct penetration mechanisms. Compared with other non-natural chemical molecules, CPPs have the advantages of good biocompatibility, low toxicity to cells, degradability after cellular transport, and direct fusion and recombinant expression with biologically active proteins, which make them an important tool for the development of drug delivery technology targeting intracellular molecules and have good prospects for application in biomedical research.

Classification

Cell-penetrating peptides can be classified according to their sequence, origin, function and mechanism of cell entry, and there is no uniform classification standard. The relatively common classification method is based on the physicochemical properties of cell-penetrating peptides, which are classified into three categories: cationic, amphiphilic and hydrophobic.

Mechanism of cellular entry of cell-penetrating peptides

It is generally believed that cell-penetrating peptides may enter the cytosol through different pathways, and these entry pathways can be broadly classified into two categories, the Endocytosis pathway and the Direct penetration pathway. It is technically not difficult to distinguish between these two entry pathways, as the fluorescence of a fluorescently labeled CPP entering a cell via the direct penetration pathway should be uniformly diffused, while the fluorescence of a CPP entering a cell via endocytosis should show a punctate distribution due to the encapsulation of vesicles. The mechanism of internalization of CPP will depend on: the nature of the peptide and substrate; the cell type, fusion, cell viability, and composition of the plasma membrane and extracellular matrix; and environmental factors such as temperature, ionic strength, and pH.

Therapeutic applications of CPP

Because of their ability to link a variety of biomolecules through covalent bonds or physical complexation, CPP have a wide range of applications. One of the most valuable is as a delivery vehicle to facilitate the effect of drugs in disease treatment. The ability to introduce drugs and other therapeutic molecules into cells gives CPP great therapeutic potential. Since its discovery, the ability of CPP to act as carriers to carry proteins or other biomolecules into cells has been continuously explored in in vitro experiments. Subsequently, in vivo experiments in mice demonstrated the ability of TAT-linked β-galactosidase to complete delivery to all mouse tissues (including the brain) after intraperitoneal injection. CPP began to be used in the treatment of many diseases as drug delivery carriers allowing drugs to enter cells and even cross the epithelial cells and blood-brain barrier.

Antibacterial and antiviral applications of CPP

Antimicrobial peptides usually have the advantages of being amphiphilic and strongly cationic, thermally stable, producing low resistance to drugs and being essentially non-toxic to eukaryotic cells. Antimicrobial peptides act on the lipid membrane of bacteria or fungi and kill microorganisms by forming pores in the membrane or increasing the permeability of the cell membrane. In addition to the direct effect on microorganisms, AMP can also control innate and adaptive immune responses by increasing the accumulation of immune cells such as macrophages and lymphocytes. More than 5,000 species of antimicrobial peptides have been identified or synthesized. Antimicrobial peptides have a strong ability to kill pathogenic microorganisms, including Gram-positive bacteria, Gram-negative bacteria, protozoa and fungi. Therefore antimicrobial peptides can be used for food and pharmaceutical applications.