Novel cell penetrating peptides with multiple motifs composed of RGD and its analogs

Mokhtarieh, Amir Abbas; Kim, Semi; Lee, Yunhee; Chung, Bong Hyun; Lee, Myung Kyu

doi:10.1016/j.bbrc.2013.01.096

Cited by 23 publications

(16 citation statements)

References 24 publications

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“…Endocytosis is a generic term for several different processes, such as phagocytosis for large particles and pinocytosis for smaller ones, as well as receptor-mediated endocytosis in which clathrin or caveolin pits are involved (Madani et al, 2011). Several receptors were uncovered to be involved in internalization of CPPs, such as chemokine receptors (Tanaka et al, 2012), syndecans (Letoha et al, 2010), neuropilins (Prud'homme and Glinka, 2012), the family of integrins (Mokhtarieh et al, 2013), homing sequences, and positively-charged scavenger receptors (Reissmann, 2014). Micropinocytosis appears to be a pathway for the MCoTI-II peptide to enter into the cell.…”

Section: Translocation Of Cpps Into Cellsmentioning

confidence: 99%

Viral and Other Cell-Penetrating Peptides as Vectors of Therapeutic Agents in Medicine

Durzyńska

Przysiecka

Nawrot

et al. 2015

J Pharmacol Exp Ther

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Efficient delivery of heterologous molecules for treatment of cells is a great challenge in modern medicine and pharmacology. Cellpenetrating peptides (CPPs) may improve efficient delivery of a wide range of macromolecular cargos, including plasmid DNA, small interfering RNA, drugs, nanoparticulate pharmaceutical carriers, and anticancer drugs. In this paper, we present the history of CPPs' discovery with special attention drawn to sequences of viral origin. We also describe different CPP families with regard to their physicochemical properties and numerous mechanisms of CPP cell uptake by direct penetration and endocytotic pathways. A detailed description is focused on formation of carrier-cargo complexes, which are needed for practical use of CPPs in medicine and biotechnology. Examples of successful application of CPPs in treatment of human diseases are also presented, including decreased tumor growth and induction of cancer cell death. Finally, we review modern design approaches to novel CPPs and prediction of their activity. To sum up, the current review presents a thorough and up-to-date knowledge of CPPs and may be a valuable source of information for researchers in pharmacology designing new therapeutic agents.

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Section: Translocation Of Cpps Into Cellsmentioning

confidence: 99%

Viral and Other Cell-Penetrating Peptides as Vectors of Therapeutic Agents in Medicine

Durzyńska

Przysiecka

Nawrot

et al. 2015

J Pharmacol Exp Ther

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“…Selective binding of CPPs to members of the integrin family leads to cell‐specific, tissue‐specific, and organ‐specific uptake . As theoretically expected for G protein‐coupled receptor (GPCR)‐ligands, uptake of their ligand fragments occurs as a lipid raft‐mediated endocytosis .…”

Section: Uptake Processesmentioning

confidence: 93%

Cell penetration: scope and limitations by the application of cell-penetrating peptides

2014

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The penetration of polar or badly soluble compounds through a cell membrane into live cells requires mechanical support or chemical helpers. Cell-penetrating peptides (CPPs) are very promising chemical helpers. Because of their low cytotoxicity and final degradation to amino acids, they are particularly favored in in vivo studies and for clinical applications. Clearly, the future of CPP research is bright; however, the required optimization studies for each drug require considerable individualized attention. Thus, CPPs are not the philosopher's stone. As of today, a large number of such transporter peptides with very different sequences have been identified. These have different uptake mechanisms and can transport different cargos. Intracellular concentrations of cargos can reach a low micromole range and are able to influence intracellular reactions. Internalized ribonucleic acids such as small interfering RNA (siRNA) and mimics of RNA such as peptide nucleic acids, morpholino nucleic acids, and triesters of oligonucleotides can influence transcription and translation. Despite the highly efficient internalization of antibodies, enzymes, and other protein factors, as well as siRNA and RNA mimics, the uptake and stabile insertion of DNA into the genome of the host cells remain substantially challenging. This review describes a wide array of differing CPPs, cargos, cell lines, and tissues. The application of CPPs is compared with electroporation, magnetofection, lipofection, viral vectors, dendrimers, and nanoparticles, including commercially available products. The limitations of CPPs include low cell and tissue selectivity of the first generation and the necessity for formation of fusion proteins, conjugates, or noncovalent complexes to different cargos and of cargo release from intracellular vesicles. Furthermore, the noncovalent complexes require a strong molar excess of CPPs, and extensive experimentation is required to determine the most optimal CPP for any given cargo and cell type. Yet to predict which CPP is optimal for any given target remains a complex question. More recently, there have been promising developments: the enhancement of cell specificity using activatable CPPs, specific transport into cell organelles by insertion of corresponding localization sequences, and the transport of drugs through blood-brain barriers, through the conjunctiva of eyes, skin, and into nerve cells. Proteins, siRNA, and mimics of oligonucleotides can be efficiently transported into cells and have been tested for treatment of certain diseases. The recent state of the art in CPP research is discussed together with the overall scope, limitations, and some recommendations for future research directions.

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“…Endocytosis is a generic term for several different processes, such as phagocytosis for large particles and pinocytosis for smaller ones, as well as receptor-mediated endocytosis in which clathrin or caveolin pits are involved [24,43,46]. Several receptors were uncovered to be involved in internalization of CPPs, such as chemokine receptors, syndecans [48,49], neuropilins [50,51], the family of integrins [52], homing sequences, and positively-charged scavenger receptors [53,54]. Micropinocytosis appears to be another pathway for some of CPPs.…”

Section: The Cytotoxicity Of the Synthesized Cpps And The Correspondimentioning

confidence: 99%

Synthesis and cellular characterization of various nano-assemblies of cell penetrating peptide-epirubicin-polyglutamate conjugates for the enhancement of antitumor activity

Mohammadi

Zakeri–Milani

Golkar

et al. 2017

Artificial Cells, Nanomedicine, and Biotechnology

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A new class of cell penetrating peptides (CPPs) named peptide amphiphile was designed to improve the intracellular uptake and antitumor activity of epirubicin (EPR). Various amphiphilic CPPs were synthesized by solid phase peptide synthesis method and were chemically conjugated to EPR. Their corresponding nanoparticles (CPPs-E4 and CPPs-E8)were prepared via non-covalent binding of the peptides and polyanions. Cytotoxicity and anti-proliferative activity were evaluated by MTT assay. Cellular uptake was examined by flow cytometry and fluorescence microscopy. The CPPs exhibited slight cytotoxicity.Binding of polyglutamate to CPPs (CPPs-E4 and CPPs-E8 nanoparticles) decreased their cytotoxicity. CPPs-E8 nanoparticles showed lower cytotoxicity than CPPs-E4 nanoparticles.Cellular uptake of K3W4K3-E8, K2W4K2-E8 and W3K4W3-E8 reached 100% with no difference between each of the mentioned CPPs and its nanoparticle at 50 µM. The antiproliferative activity of EPR was enhanced following conjugation to peptides and nanoparticles at 25 µM. CPPs-EPR-E4 and -E8 nanoparticles displayed higher antiproliferative activity than CPPs-EPR at 25 µM. CPPs-E8-EPR nanoparticles showed higher anti-proliferative activity than CPPs-E4-EPR. K3W4K3-E8-EPR nanoparticles exhibited the highest anti-proliferative activity at 25 µM. The synthesized peptide nanoparticles are proposed as suitable carriers for improving the intracellular delivery of EPR into tumor cells with low cytotoxicity and high antitumor activity.

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Novel cell penetrating peptides with multiple motifs composed of RGD and its analogs

Cited by 23 publications

References 24 publications

Viral and Other Cell-Penetrating Peptides as Vectors of Therapeutic Agents in Medicine

Viral and Other Cell-Penetrating Peptides as Vectors of Therapeutic Agents in Medicine

Cell penetration: scope and limitations by the application of cell-penetrating peptides

Synthesis and cellular characterization of various nano-assemblies of cell penetrating peptide-epirubicin-polyglutamate conjugates for the enhancement of antitumor activity

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