Cell-penetrating peptides as vectors for peptide, protein and oligonucleotide delivery

Mäe, Maarja Andaloussi; Langel, Ülo

doi:10.1016/j.coph.2006.04.004

Cited by 293 publications

(166 citation statements)

References 42 publications

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“…CPPs though a short stretch of amino acids (e.g., HIV-1 Tat basic domain is only nine amino acid in length) have the capacity to deliver a macromolecular cargo that is 100-fold higher in molecular weight than their own. Macromolecules, such as proteins, plasmids, siRNA, nanoparticles, PNAs, and liposomes, that are otherwise impermeable to the plasma membrane have been translocated into the cells as cargo complex with CPPs (1). In the evergrowing class of CPPs, HIV-1 Tat basic domain and polyarginines have been used extensively for macromolecule delivery.…”

Section: Introductionmentioning

confidence: 99%

Cell‐penetrating peptides: Nanocarrier for macromolecule delivery in living cells

2010

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SummaryNovel classes and applications of cell-penetrating peptides (CPPs) are being constantly discovered since they were first identified 2 decades ago. These short cationic peptides (nanomolecules) either by covalent binding or by noncovalent binding can traverse cell membranes and deliver a variety of molecules that are unable to overcome the permeability barrier in their own capacity. The ability of the CPPs to deliver variety of macromolecules, such as oligonucleotides, therapeutic drugs, proteins, and medical imaging agents, by forming nanoparticulate carriers in a range of cells has led them to emerge as a potential tool for both macromolecule delivery application and to gain insight into the fundamentals of mechanism of cellular uptake across the plasma membrane. This review explores the recent advances, challenges, and future prospects in the field of CPP-mediated cargo delivery in mammalian and plant cells. Studies have been conducted into the peptide chemistry and stability of CPP-macromolecular complexes. Most of the CPPs have been shown to be nontoxic and do not interfere with the functionality of the macromolecules delivered across the cell membrane. The mechanism of uptake of CPP-cargo complexes and the uptake of CPPs alone across the plasma membrane remains unresolved. As the world of CPPs is rapidly advancing in both mammalian and plant system, there is a promising future for the various applications of transduction and transfection into intact cells.

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Section: Introductionmentioning

confidence: 99%

Cell‐penetrating peptides: Nanocarrier for macromolecule delivery in living cells

2010

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“…It is regarded as a good carrier of target proteins, peptide, DNA, small interfering RNA, etc. Although the internalization mechanism of CPPs is still extensively debatable, the applications of them are becoming more and more popular (40). Here, we used a well-known CPP TAT as the vehicle for the peptide delivery.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the met receptor tyrosine kinase signaling enhances the chemosensitivity of glioma cell lines to CDDP through activation of p38 MAPK pathway

Lou

Zhou

Yin

et al. 2009

Molecular Cancer Therapeutics

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The Met receptor tyrosine kinase is known to be overexpressed in many solid tumors and plays a crucial role in tumor invasive growth and metastasis. In this study, we showed that hepatocyte growth factor-induced Met activation as well as Met-dependent downstream signaling of AKT and p44/42 mitogen-activated protein kinase (MAPK) could be efficiently blocked by TAT-coupled carboxyl-terminal tail peptide of Met receptor (TCTP), and inactivation of Met signaling significantly enhanced the sensitivity of T98G and U251 glioma cells to cisdiaminedichloroplatinum (CDDP, cisplatin). However, neither phosphoinositide 3-kinase/AKT inhibitor LY294002 nor p44/42 MAPK inhibitor PD98059 alone or combined could imitate the effect of TCTP on chemosensitivity enhancement of T98G cells to CDDP, indicating that Met-dependent inactivation of AKT and p44/42 MAPK signaling was not the main cause for the increased chemosensitivity to CDDP. Further studies revealed that TCTP significantly activated p38 MAPK in T98G and U251 cell lines. Activation of p38 MAPK by sorbitol pretreatment resembled the sensitization effects, whereas inhibition of p38 MAPK activation by its inhibitor SB202190 counteracted the sensitization effects induced by TCTP. Therefore, p38 MAPK activation was one of the major causes for the increased chemosensitivity to CDDP induced by Met inactivation. Taken together, the study indicated that Met receptor played an important role in regulating cell response to chemotherapy and suggested that inhibition of Met signaling could be used in combination with other chemotherapeutic regimens in treatment of tumor patients.

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“…Bio‐macromolecules such as DNA, RNA, and proteins are considered to be potential biomedical reagents for the control of selective biological reactions 1. Since most bio‐macromolecules have difficulty penetrating cells through their plasma membranes, various methodologies based on viral and nonviral delivery systems have been applied for the intracellular delivery of bio‐macromolecules 2.…”

Section: Introductionmentioning

confidence: 99%

Multimeric Amphipathic α‐Helical Sequences for Rapid and Efficient Intracellular Protein Transport at Nanomolar Concentrations

Chong

Nam

et al. 2018

Advanced Science

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An amphipathic leucine (L) and lysine (K)‐rich α‐helical peptide is multimerized based on helix‐loop‐helix structures to maximize the penetrating activities. The multimeric LK‐based cell penetrating peptides (LK‐CPPs) can penetrate cells as protein‐fused forms at 100–1000‐fold lower concentrations than Tat peptide. The enhanced penetrating activity is increased through multimerization by degrees up to the tetramer level. The multimeric LK‐CPPs show rapid cell penetration through macropinocytosis at low nanomolar concentrations, unlike the monomeric LK, which have slower penetrating kinetics at much higher concentrations. The heparan sulfate proteoglycan (HSPG) receptors are highly involved in the rapid internalization of multimeric LK‐CPPs. As a proof of concept of biomedical applications, an adipogenic transcription factor, peroxisome proliferator‐activated receptor gamma 2 (PPAR‐γ 2), is delivered into preadipocytes, and highly enhanced expression of adipogenic genes at nanomolar concentrations is induced. The multimeric CPPs can be a useful platform for the intracellular delivery of bio‐macromolecular reagents that have difficulty with penetration in order to control biological reactions in cells at feasible concentrations for biomedical purposes.

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Cell-penetrating peptides as vectors for peptide, protein and oligonucleotide delivery

Cited by 293 publications

References 42 publications

Cell‐penetrating peptides: Nanocarrier for macromolecule delivery in living cells

Cell‐penetrating peptides: Nanocarrier for macromolecule delivery in living cells

Inhibition of the met receptor tyrosine kinase signaling enhances the chemosensitivity of glioma cell lines to CDDP through activation of p38 MAPK pathway

Multimeric Amphipathic α‐Helical Sequences for Rapid and Efficient Intracellular Protein Transport at Nanomolar Concentrations

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