Martin Matijass

Bio: Martin Matijass is an academic researcher from University of Cologne. The author has an hindex of 1, co-authored 1 publications receiving 1 citations.

Cell-penetrating peptides as part of therapeutics used in cancer research

Abstract: Peptides have gained more and more interest as therapeutics for different fields of medical indications. Built up via a peptide bond from naturally occurring amino acids they stand out by their high target selectivity and good biocompatibility. However, using chemical peptide synthesis also modifications are easily introduced and offer various opportunities to fine-tune their activity spectrum. One of the main areas of the global peptide market is oncology and during the past years, many peptide therapeutics with anti-tumor activity have been reported that evoke metastasis in malignant cells or evasion of cell death. Cell-penetrating peptides (CPPs) are a particular group of bioactive peptides that can be naturally or synthetically derived and have the ability to autonomously translocate in cells and transport various cargoes with them. These versatile carriers have been widely used to deliver different kinds of therapeutic molecules, and have also found application in cancer research. Within this review we will summarize recent efforts made in this direction with a focus on the specific cancer indications for which CPP-related therapeutics have been developed and studied.

Development of a novel PTD-mediated IVT-mRNA delivery platform for potential protein replacement therapy of metabolic/genetic disorders.

Abstract: The potential clinical applications of the powerful in vitro-transcribed (IVT)-mRNAs, to restore defective protein functions, strongly depend on their successful intracellular delivery and transient translation through the development of safe and efficient delivery platforms. In this study, an innovative (international patent-pending) methodology was developed, combining the IVT-mRNAs with the protein transduction domain (PTD) technology, as an efficient delivery platform. Based on the PTD technology, which enables the intracellular delivery of various cargoes intracellularly, successful conjugation of a PTD to the IVT-mRNAs was achieved and evaluated by band-shift assay and NMR spectroscopy. In addition, the PTD-IVT-mRNAs were applied and evaluated in two protein-disease models, including the mitochondrial disorder fatal infantile cardioencephalomyopathy and cytochrome c oxidase (COX) deficiency (attributed to SCO2 gene mutations) and β-thalassemia. The PTD-IVT-mRNA of SCO2 was successfully transduced and translated to the corresponding Sco2 protein inside the primary fibroblasts of a SCO2/COX-deficient patient, whereas the PTD-IVT-mRNA of β-globin was transduced and translated in bone marrow cells, derived from three β-thalassemic patients. The transducibility and the structural stability of the PDT-IVT-mRNAs, in both cases, were confirmed at the RNA and protein levels. We propose that our novel delivery platform could be clinically applicable as a protein therapy for metabolic/genetic disorders.

Approaches for evaluation of novel CPP-based cargo delivery systems

Abstract: Cell penetrating peptides (CPPs) can be broadly defined as relatively short synthetic, protein derived or chimeric peptides. Their most remarkable property is their ability to cross cell barriers and facilitate the translocation of cargo, such as drugs, nucleic acids, peptides, small molecules, dyes, and many others across the plasma membrane. Over the years there have been several approaches used, adapted, and developed for the evaluation of CPP efficacies as delivery systems, with the fluorophore attachment as the most widely used approach. It has become progressively evident, that the evaluation method, in order to lead to successful outcome, should concede with the specialties of the delivery. For characterization and assessment of CPP-cargo a combination of research tools of chemistry, physics, molecular biology, engineering, and other fields have been applied. In this review, we summarize the diverse, in silico, in vitro and in vivo approaches used for evaluation and characterization of CPP-based cargo delivery systems.

Cell-Penetrating Peptides as Passive Permeation Enhancers for Transdermal Drug Delivery

Abstract: Cell-penetrating peptides have been widely used as a tool to gain access to cytosol for numerous applications. The review highlights the advances made in preclinical and clinical research using cell-penetrating peptides since their discovery in 1980s. Further, the emphasis is on summarizing the role of cell-penetrating peptides as permeation enhancers for transdermal and topical drug delivery applications. A summary table of preclinical studies utilizing various peptides in combination with different active ingredients and drug delivery systems is included. Lastly, we capture the challenges associated with the cell-penetrating peptides to translate the preclinical work to clinical applications.

Lipid-Specific Direct Translocation of the Cell-Penetrating Peptide NAF-1^44–67 across Bilayer Membranes

Abstract: The cell-penetrating peptide NAF-1 has recently emerged as a promising candidate for selective penetration and destruction of cancer cells. It displays numerous membrane-selective behaviors including cell-specific uptake and organelle-specific degradation. In this work, we explore membrane penetration and translocation of NAF-1 in model lipid bilayer vesicles as a function of lipid identity in zwitterionic phosphatidylcholine lipids mixed with anionic phosphatidylserine, phosphatidylglycerol, and phosphatidic acid lipids. By monitoring the digestion of NAF-1 using the protease trypsin located inside but not outside the vesicles, we determined that the translocation of NAF-1 was significantly enhanced by the presence of phosphatidic acid in the membrane compared to the other three anionic or zwitterionic lipids. These findings were correlated to fluorescence measurements of dansyl-labeled NAF-1, which revealed whether noncovalent interactions between NAF-1 and the bilayer were most stable either at the membrane/solution interface or within the membrane interior. Phosphatidic acid promoted interactions with fatty acid tails, while phosphatidylcholine, phosphatidylserine, and phosphatidylglycerol stabilized interactions with polar lipid headgroups. Interfacial vibrational sum frequency spectroscopy experiments revealed that the phosphate moiety on phosphatidic acid headgroups was better hydrated than on the other three lipids, which helped to shuttle NAF-1 into the hydrophobic region. Our findings demonstrate that permeation does not depend on the net charge on phospholipid lipid headgroups in these model vesicles and suggest a model wherein NAF-1 crosses membranes selectively due to lipid-specific interactions at bilayer surfaces.