Cell penetrating peptides: intracellular pathways and pharmaceutical perspectives.
ABSTRACT Cell penetrating peptides, generally categorized as amphipathic or cationic depending on their sequence, are increasingly drawing attention as a non-invasive delivery technology for macromolecules. Delivery of a diverse set of cargo in terms of size and nature ranging from small molecules to particulate cargo has been attempted using different types of cell penetrating peptides (CPPs) in vitro and in vivo. However, the internalization mechanism of CPPs is an unresolved issue to date, with dramatic changes in view regarding the involvement of endocytosis as a pathway of internalization. A key reason for the lack of consensus on the mechanism can be attributed to the methodology in deciphering the internalization mechanism. In this review, we highlight some of the methodology concerns, focus more on the internalization pathway and also provide a novel perspective about the intracellular processing of CPPs, which is a crucial aspect to consider when selecting a cell penetrating peptide as a drug delivery system. In addition, recent applications of cell penetrating peptides for the delivery of small molecules, peptides, proteins, oligonucleotides, nanoparticles and liposomes have been reviewed.
- SourceAvailable from: Ana M Carmona-Ribeiro
Dataset: ijms-62363 (6)
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ABSTRACT: Microparticles (MPs) and nanoparticles (NPs) have received considerable attention for the design of drug delivery systems (DDS) with unique properties owing to the increased surface area and the ability to fine tune the release process. More recently, a new type of DDS that capitalize on the advantages of both NPs and MPs has been introduced. Nanoparticle-in-Microparticle Delivery Systems (NiMDS) comprise the encapsulation of NPs within MPs and lead to features that are unique and different from those of the individual components. These technology platforms can be produced employing from conventional to more sophisticated methodologies and equipment and they are administered by different routes such as oral, pulmonary or even parenteral. Moreover, if designed appropriately, “they can (i) protect drug payloads and prevent physical and chemical instability phenomena in the biological environment, (ii) improve the release profile of the encapsulated agent, (iii) reduce or eliminate the burst effect and (iv) target specific cells, tissues and organs.” Should be changed to “they can protect drug payloads and prevent physical and chemical instability phenomena in the biological environment, improve the release profile of the encapsulated agent, reduce or eliminate the burst effect and target specific cells, tissues and organs.”Journal of Biomaterials and Tissue Engineering. 02/2013; 3(1):22-38.
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ABSTRACT: Multiple substitution of d- for l-amino acids decreases the intracellular uptake of cationic cell penetrating peptides (CPP) in a cell line-dependent manner. We show here that a single d-amino acid substitution can decrease the overall uptake of the anionic, amphipathic CPP, p28, into cancer and histologically matched normal cell lines, while not altering the preferential uptake of p28 into cancer cells. The decrease appears dependent on the position of the d-substitution within the peptide and the ability of the substituted d-amino acid to alter chirality. We also suggest that when d-substitution alters the ratio of α-helix to β-sheet content of an anionic CPP, its translocation across the cell membrane is altered, reducing overall entry. These observations may have a significant effect on the design of future d-substituted analogues of cell penetrating peptides.Molecular Pharmaceutics 12/2014; · 4.79 Impact Factor