Department of Biomaterials and Healthcare, Division of Life Science and Bioprocesses, Fraunhofer Institute for Applied Polymer Research (IAP), Geiselbergstraße 69, 14476 Potsdam-Golm, Germany
Prof. Dr. Joachim Storsberg
Department of Biomaterials and Healthcare, Division of Life Science and Bioprocesses, Fraunhofer Institute for Applied Polymer Research (IAP), Geiselbergstraße 69, 14476 Potsdam-Golm, Germany
Interactions between glycans and proteins have tremendous impact in biomolecular interactions. They are important for cell–cell interactions, proliferation and much more. Here, we emphasize the glycan-mediated interactions between pathogens and host cells. Pseudomonas aeruginosa, responsible for a huge number of nosocomial infections, is especially the focus when it comes to glycan-derivatives as pathoblockers. We present a microwave assisted protecting group free synthesis of glycomonomers based on lactose, melibiose and fucose. The monomers were polymerized in a precipitation polymerization in the presence of NiPAm to form crosslinked glyco-nanogels. The influence of reaction parameters like crosslinker type or stabilizer amount was investigated. The gels were characterized in lectin binding studies using model lectins and showed size and composition-dependent inhibition of lectin binding. Due to multivalent presentation of glycans in the gel, the inhibition was clearly stronger than with unmodified saccharides, which was compared after determination of the glycan loading. First studies with Pseudomonas aeruginosa revealed a surprising influence on the secretion of virulence factors. Functional glycogels may be in the future potent alternatives or adjuvants for antibiotic treatment of infections based on glycan interactions between host and pathogen.
Nanomedicine helps to fight diseases at the cellular and molecular level by utilizing unique properties of quasi-atomic particles at a size scale ranging from 1 to 100 nm. Nanoparticles are used in therapeutic and diagnostic approaches, referred to as theranostics. The aim of this review is to illustrate the application of general principles of nanotechnology to select examples of life sciences, molecular medicine and bio-assays. Critical aspects relating to those examples are discussed.
Cancer patients are at a very high risk of serious thrombotic events, often fatal. The causes discussed include the detachment of thrombogenic particles from tumor cells or the adverse effects of chemotherapeutic agents. Cytostatic agents can either act directly on their targets or, in the case of a prodrug approach, require metabolization for their action. Cyclophosphamide (CPA) is a widely used cytostatic drug that requires prodrug activation by cytochrome P450 enzymes (CYP) in the liver. We hypothesize that CPA could induce thrombosis in one of the following ways: (1) damage to endothelial cells (EC) after intra-endothelial metabolization; or (2) direct damage to EC without prior metabolization. In order to investigate this hypothesis, endothelial cells (HUVEC) were treated with CPA in clinically relevant concentrations for up to 8 days. HUVECs were chosen as a model representing the first place of action after intravenous CPA administration. No expression of CYP2B6, CYP3A4, CYP2C9 and CYP2C19 was found in HUVEC, but a weak expression of CYP2C18 was observed. CPA treatment of HUVEC induced DNA damage and a reduced formation of an EC monolayer and caused an increased release of prostacyclin (PGI2) and thromboxane (TXA) associated with a shift of the PGI2/TXA balance to a prothrombotic state. In an in vivo scenario, such processes would promote the risk of thrombus formation.
Cellulosic substrates are known for their biocompatibility, non-cytotoxicity, hypoallergenicity and sterilizability. It is therefore desirable to have a bundle of methods to equip them with tailored properties such as affinity profiles for various applications. In the case of highly swelling materials such as cellulose sponges, “dry” functionalization using plasma activation is the method of choice. The purpose of the study was to adapt low-pressure plasma technology for targeted cellulose modification. Using plasma (pre-) treatment combined with gaseous reactants like O2, ethylene oxide or silane, three different cellulose modifications were obtained and characterized by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). Swelling measurements and bacterial adhesion tests revealed distinctive material properties compared to educt. The development of these non-aqueous methods demonstrated an effective procedural route towards modified cellulosic materials for usage in wound dressing, micro patterned assays or bacterial filtration.