TY - JOUR A1 - Donskyi, Ievgen A1 - Nie, C. A1 - Ludwig, K. A1 - Trimpert, J. A1 - Ahmed, R. A1 - Quaas, E. A1 - Achazi, K. A1 - Radnik, Jörg A1 - Adeli, M. A1 - Haag, R. A1 - Osterrieder, K. T1 - Graphene Sheets with Defined Dual Functionalities for the Strong SARS-CoV-2 Interactions N2 - Search of new strategies for the inhibition of respiratory viruses is one of the urgent health challenges worldwide, as most of the current therapeutic agents and treatments are inefficient. Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) has caused a pandemic and has taken lives of approximately two Million people to date. Even though various vaccines are currently under development, virus, and especially its spike glycoprotein can mutate, which highlights a Need for a broad-spectrum inhibitor. In this work, inhibition of SARS-CoV-2 by graphene platforms with precise dual sulfate/alkyl functionalities is investigated. A series of graphene derivatives with different lengths of aliphatic chains is synthesized and is investigated for their ability to inhibit SARS-CoV-2 and feline coronavirus. Graphene derivatives with long alkyl chains (>C9) inhibit coronavirus replication by virtue of disrupting viral envelope. The ability of these graphene platforms to rupture viruses is visualized by atomic force microscopy and cryogenic electron microscopy. A large concentration window (10 to 100-fold) where graphene platforms display strongly antiviral activity against native SARS-CoV-2 without significant toxicity against human cells is found. In this concentration range, the synthesized graphene platforms inhibit the infection of enveloped viruses efficiently, opening new therapeutic and metaphylactic avenues against SARS-CoV-2. KW - Graphene KW - Graphene-based polyglycerol sulfates KW - SARS-CoV2 inhibitor KW - Virucidality PY - 2021 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-520858 DO - https://doi.org/10.1002/smll.202007091 VL - 17 IS - 11 SP - 7091 PB - Wiley VCH AN - OPUS4-52085 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Page, T.M. A1 - Nie, C. A1 - Neander, L. A1 - Povolotsky, T.L. A1 - Sahoo, A.K. A1 - Nickl, Philip A1 - Adler, J.M. A1 - Bawadkji, O. A1 - Radnik, Jörg A1 - Achazi, K. A1 - Ludwig, K. A1 - Lauster, D. A1 - Netz, R.R. A1 - Trimpert, J. A1 - Kaufer, B. A1 - Haag, R. A1 - Donskyi, Ievgen T1 - Functionalized Fullerene for Inhibition of SARS-CoV-2 Variants N2 - As virus outbreaks continue to pose a challenge, a nonspecific viral inhibitor can provide significant benefits, especially against respiratory viruses. Polyglycerol sulfates recently emerge as promising agents that mediate interactions between cells and viruses through electrostatics, leading to virus inhibition. Similarly, hydrophobic C60 fullerene can prevent virus infection via interactions with hydrophobic cavities of surface proteins. Here, two strategies are combined to inhibit infection of SARS-CoV-2 variants in vitro. Effective inhibitory concentrations in the millimolar range highlight the significance of bare fullerene’s hydrophobic moiety and electrostatic interactions of polysulfates with surface proteins of SARS-CoV-2. Furthermore, microscale thermophoresis measurements support that fullerene linear polyglycerol sulfates interact with the SARS-CoV-2 virus via its spike protein, and highlight importance of electrostatic interactions within it. All-atom molecular dynamics simulations reveal that the fullerene binding site is situated close to the receptor binding domain, within 4 nm of polyglycerol sulfate binding sites, feasibly allowing both portions of the material to interact simultaneously. KW - Covalent functionalization KW - Fullerene KW - SARS-CoV 2 KW - Sulfated materials KW - Virus inhibition PY - 2023 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-568672 DO - https://doi.org/10.1002/smll.202206154 SN - 1613-6810 SP - 1 EP - 8 PB - Wiley VCH AN - OPUS4-56867 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Donskyi, Ievgen A1 - Drüke, M. A1 - Silberreis, K. A1 - Lauster, D. A1 - Ludwig, K. A1 - Kühne, C. A1 - Unger, Wolfgang A1 - Böttcher, C. A1 - Herrmann, A. A1 - Dernedde, J. A1 - Adeli, M. A1 - Haag, R. T1 - Interactions of fullerene-polyglycerol sulfates at viral and cellular interfaces N2 - Understanding the mechanism of interactions of nanomaterials at biointerfaces is a crucial issue to develop new antimicrobial vectors. In this work, a series of water-soluble fullerene-polyglycerol sulfates (FPS) with different fullerene/polymer weight ratios and varying numbers of polyglycerol sulfate branches are synthesized, characterized, and their interactions with two distinct surfaces displaying proteins involved in target cell recognition are investigated. The combination of polyanionic branches with a solvent exposed variable hydrophobic core in FPS proves to be superior to analogs possessing only one of these features in preventing interaction of vesicular Stomatitis virus coat glycoprotein (VSV-G) with baby hamster kidney cells serving as a model of host cell. Interference with L-selectin-ligand binding is dominated by the negative charge, which is studied by two assays: a competitive surface plasmon resonance (SPR)-based inhibition assay and the leukocyte cell (NALM-6) rolling on ligands under flow conditions. Due to possible intrinsic hydrophobic and electrostatic effects of synthesized compounds, pico- to nanomolar half maximal inhibitory concentrations (IC50) are achieved. With their highly antiviral and anti-inflammatory properties, together with good biocompatibility, FPS are promising candidates for the future development towards biomedical applications. KW - Fullerene-Polyglycerol Sulfates KW - Fullerene KW - Biointerfaces KW - XPS PY - 2018 DO - https://doi.org/10.1002/smll.201800189 SN - 1613-6829 SN - 1613-6810 VL - 14 IS - 17 SP - 1800189, 1 EP - 7 PB - WILEY-VCH Verlag GmbH & Co. KGaA CY - Weinheim AN - OPUS4-44573 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Tan, K. H. A1 - Sattari, S. A1 - Beyranvand, S. A1 - Faghani, A. A1 - Ludwig, K. A1 - Schwibbert, Karin A1 - Böttcher, C. A1 - Haag, R. A1 - Adeli, M. T1 - Thermoresponsive Amphiphilic Functionalization of Thermally Reduced Graphene Oxide to Study Graphene/Bacteria Hydrophobic Interactions N2 - An understanding of the interactions of 2D nanomaterials with pathogens is of vital importance to developing and controlling their antimicrobial properties. In this work, the interaction of functionalized graphene with tunable hydrophobicity and bacteria is investigated. Poly-(ethylene glycol)-block-(poly-N-isopropylacrylamide) copolymer (PEG-b-PNIPAM) with the triazine joint point was attached to the graphene Surface by a nitrene [2 + 1] cycloaddition reaction. By thermally switching between hydrophobic and hydrophilic states, functionalized graphene sheets were able to bind to bacteria. Bacteria were eventually disrupted when the functionality was switched to the hydrophobic state. On the basis of measuring the different microscopy methods and a live/dead viability assay, it was found that Escherichia coli (E. coli) bacteria are more susceptible to hydrophobic interactions than B. cereus bacteria, under the same conditions. Our investigations confirm that hydrophobic interaction is one of the main driving forces at the presented graphene/bacteria interfaces and promotes the antibacterial activity of graphene derivatives significantly. KW - 2D nanomaterials KW - Functionalized graphene KW - Antimicrobial KW - Hydrophobic interaction PY - 2019 DO - https://doi.org/10.1021/acs.langmuir.8b03660 VL - 35 IS - 13 SP - 4736 EP - 4746 PB - ACS Publications AN - OPUS4-49235 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Neffe, A.T. A1 - Von Ruesten-Lange, M. A1 - Braune, S. A1 - Lützow, K. A1 - Roch, T. A1 - Richau, K. A1 - Krüger, A. A1 - Becherer, T. A1 - Thünemann, Andreas A1 - Jung, F. A1 - Haag, R. A1 - Lendlein, A. T1 - Multivalent grafting of hyperbranched oligo- and polyglycerols shielding rough membranes to mediate hemocompatibility N2 - Hemocompatible materials are needed for internal and extracorporeal biomedical applications, which should be realizable by reducing protein and thrombocyte adhesion to such materials. Polyethers have been demonstrated to be highly efficient in this respect on smooth surfaces. Here, we investigate the grafting of oligo- and polyglycerols to rough poly(ether imide) membranes as a polymer relevant to biomedical applications and show the reduction of protein and thrombocyte adhesion as well as thrombocyte activation. It could be demonstrated that, by performing surface grafting with oligo- and polyglycerols of relatively high polydispersity (>1.5) and several reactive groups for surface anchoring, full surface shielding can be reached, which leads to reduced protein adsorption of albumin and fibrinogen. In addition, adherent thrombocytes were not activated. This could be clearly shown by immunostaining adherent proteins and analyzing the thrombocyte covered area. The presented work provides an important strategy for the development of application relevant hemocompatible 3D structured materials. KW - Nanotechnology KW - thrombocyte adhesion KW - biomedical applications PY - 2014 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-308196 DO - https://doi.org/10.1039/c4tb00184b SN - 2050-750X SN - 2050-7518 VL - 2 IS - 23 SP - 3626 EP - 3635 PB - Royal Soc. of Chemistry CY - Cambridge AN - OPUS4-30819 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Mohammadifar, E. A1 - Ahmadi, V. A1 - Gholami, M.F. A1 - Oehrl, A. A1 - Kolyvushko, O. A1 - Nie, C. A1 - Donskyi, Ievgen A1 - Herziger, S. A1 - Radnik, Jörg A1 - Ludwig, K. A1 - Böttcher, C. A1 - Rabe, J.P. A1 - Osterrieder, K. A1 - Azab, W. A1 - Haag, R. A1 - Adeli, M. T1 - Graphene-Assisted Synthesis of 2D Polyglycerols as Innovative Platforms for Multivalent Virus Interactions N2 - 2D nanomaterials have garnered widespread attention in biomedicine and bioengineering due to their unique physicochemical properties. However, poor functionality, low solubility, intrinsic toxicity, and nonspecific interactions at biointerfaces have hampered their application in vivo. Here, biocompatible polyglycerol units are crosslinked in two dimensions using a graphene-assisted strategy leading to highly functional and water-soluble polyglycerols nanosheets with 263 ± 53 nm and 2.7 ± 0.2 nm average lateral size and thickness, respectively. A single-layer hyperbranched polyglycerol containing azide functional groups is covalently conjugated to the surface of a functional graphene template through pH-sensitive linkers. Then, lateral crosslinking of polyglycerol units is carried out by loading tripropargylamine on the surface of graphene followed by lifting off this reagent for an on-face click reaction. Subsequently, the polyglycerol nanosheets are detached from the surface of graphene by slight acidification and centrifugation and is sulfated to mimic heparin sulfate proteoglycans. To highlight the impact of the two-dimensionality of the synthesized polyglycerol sulfate nanosheets at nanobiointerfaces, their efficiency with respect to herpes Simplex virus type 1 and severe acute respiratory syndrome corona virus 2 inhibition is compared to their 3D nanogel analogs. Four times stronger in virus Inhibition suggests that 2D polyglycerols are superior to their current 3D counterparts.2D nanomaterials have garnered widespread attention in biomedicine and bioengineering due to their unique physicochemical properties. However, poor functionality, low solubility, intrinsic toxicity, and nonspecific interactions at biointerfaces have hampered their application in vivo. Here, biocompatible polyglycerol units are crosslinked in two dimensions using a graphene-assisted strategy leading to highly functional and water-soluble polyglycerols nanosheets with 263 ± 53 nm and 2.7 ± 0.2 nm average lateral size and thickness, respectively. A single-layer hyperbranched polyglycerol containing azide functional groups is covalently conjugated to the surface of a functional graphene template through pH-sensitive linkers. Then, lateral crosslinking of polyglycerol units is carried out by loading tripropargylamine on the surface of graphene followed by lifting off this reagent for an on-face click reaction. Subsequently, the polyglycerol nanosheets are detached from the surface of graphene by slight acidification and centrifugation and is sulfated to mimic heparin sulfate proteoglycans. To highlight the impact of the two-dimensionality of the synthesized polyglycerol sulfate nanosheets at nanobiointerfaces, their efficiency with respect to herpes Simplex virus type 1 and severe acute respiratory syndrome corona virus 2 inhibition is compared to their 3D nanogel analogs. Four times stronger in virus Inhibition suggests that 2D polyglycerols are superior to their current 3D counterparts. KW - 2D Materials KW - Graphene template KW - Multivalency KW - Polyglycerol KW - Virus inhibition PY - 2021 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-527726 DO - https://doi.org/10.1002/adfm.202009003 VL - 31 IS - 32 SP - 2009003 PB - Wiley VCH AN - OPUS4-52772 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Markwart, J. C. A1 - Battig, Alexander A1 - Urbaniak, T. A1 - Haag, K. A1 - Koschek, K. A1 - Schartel, Bernhard A1 - Wurm, F. R. T1 - Intrinsic flame retardant phosphonate-based vitrimers as a recyclable alternative for commodity polymers in composite materials N2 - Recycling of crosslinked fiber-reinforced polymers is difficult. Moreover, as they are often based on flammable resins, additional additives are needed. So-called “vitrimers” open the possibility of Recycling and reprocessing and repairing with dynamically crosslinked chemistries. To date, vitrimer-based composites still need flame retardant additives, such as organophosphates. An additive-free vitrimer composite has not been reported. Herein, we synthesized an intrinsic flame-retardant vitrimer, relying on vinylogous polyurethanes containing covalently installed phosphonates as flame-retardant units and prepared glassfiber-reinforced composites. We studied recycling and flame retardant properties and compared the data to phosphorus-free vitrimers and conventional epoxy resins (with and without additive flame retardant). Our phosphonate-based vitrimer proved in first tests, a flame retardant effect comparable to commercial flame retardant resins. The bending strength and bending modulus for the phosphorus-vitrimer glass fiber composites were comparable to glass fiber composites with permanently cross-linked epoxies. In summary, we were able to prove that the covalent installation of phosphonates into vitrimers allows the preparation of recyclable and intrinsic flame retardant composites that do not need flame retardant additives. We believe this concept can be expanded to other polymer networks and additives to generate recyclable and sustainable high-performance materials. KW - Vitrimer KW - Flame retardant KW - Recyclable KW - Organophosphonate KW - Polyurethane PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-510889 DO - https://doi.org/10.1039/d0py00275e VL - 11 IS - 30 SP - 4933 EP - 4941 AN - OPUS4-51088 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Lukowiak, M.C. A1 - Wettmarshausen, Sascha A1 - Hidde, Gundula A1 - Landsberger, Petra A1 - Boenke, Viola A1 - Rodenacker, K. A1 - Braun, Ulrike A1 - Friedrich, Jörg Florian A1 - Gorbushina, Anna A1 - Haag, R. T1 - Polyglycerol coated polypropylene surfaces for protein and bacteria resistance N2 - Polyglycerol (PG) coated polypropylene (PP) films were synthesized in a two-step approach that involved plasma bromination and subsequently grafting hyperbranched polyglycerols with very few amino functionalities. The influence of different molecular weights and density of reactive linkers were investigated for the grafted PGs. Longer bromination times and higher amounts of linkers on the surface afforded long-term stability. The protein adsorption and bacteria attachment of the PP-PG films were studied. Their extremely low amine content proved to be beneficial for preventing bacteria attachment. PY - 2015 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-325406 DO - https://doi.org/10.1039/c4py01375a SN - 1759-9954 SN - 1759-9962 VL - 6 IS - 8 SP - 1350 EP - 1359 AN - OPUS4-32540 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Wu, C. A1 - Schwibbert, Karin A1 - Achazi, K. A1 - Landsberger, Petra A1 - Gorbushina, Anna A1 - Haag, R. T1 - Active antibacterial and antifouling surface coating via a facile one-step enzymatic cross-linking N2 - Prevention of microbial contamination of surfaces is one of the biggest challenges for biomedical applications. Establishing a stable, easily produced, highly antibacterial surface coating offers an efficient solution but remains a technical difficulty. Here, we report on a new approach to create an in situ hydrogel film-coating on glass surfaces made by enzymatic cross-linking under physiological conditions. The cross-linking is catalyzed by horseradish peroxidase (HRP)/glucose oxidase (GOD)-coupled cascade reactions in the presence of glucose and results in 3D dendritic polyglycerol (dPG) scaffolds bound to the surface of glass. These scaffolds continuously release H2O2 as long as glucose is present in the system. The resultant polymeric coating is highly stable, bacterial-repellent, and functions under physiological conditions. Challenged with high loads of bacteria (OD540 = 1.0), this novel hydrogel and glucose-amended coating reduced the cell viability of Pseudomonas putida (Gram-negative) by 100% and Staphylococcus aureus (Gram-positive) by ≥40%, respectively. Moreover, glucose-stimulated production of H2O2 by the coating system was sufficient to kill both test bacteria (at low titers) with >99.99% Efficiency within 24 h. In the presence of glucose, this platform produces a coating with high effectiveness against bacterial adhesion and survival that can be envisioned for the applications in the glucose-associated medical/oral devices. KW - Antifouling KW - Surface coating KW - Biofilm KW - Bacterial adhesion PY - 2017 DO - https://doi.org/10.1021/acs.biomac.6b01527 SN - 1525-7797 SN - 1526-4602 VL - 18 IS - 1 SP - 210 EP - 216 AN - OPUS4-39003 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Pauli, Jutta A1 - Wycisk, V. A1 - Welker, P. A1 - Justies, A. A1 - Resch-Genger, Ute A1 - Haag, R. A1 - Licha, K. T1 - Glycerol-Based Contrast Agents: A Novel Series of Dendronized Pentamethine Dyes N2 - The synthesis of water-soluble dyes, which absorb and emit in the range between 650 and 950 nm and display high extinction coefficients (ε) as well as high fluorescence quantum yields (Φf), is still a demand for optical imaging. We now present a synthetic route for the preparation of a new group of glycerol-substituted cyanine dyes from dendronized indole precursors that have been functionalized as Nhydroxysuccinimide (NHS) esters. High Φf values of up to 0.15 and extinction coefficients of up to 189 000 L mol−1 cm−1 were obtained for the pure dyes. Furthermore, conjugates of the new dendronized dyes with the antibody cetuximab (ctx) that were directed against the epidermal growth factor receptor (EGFR) of tumor cells could be prepared with dye to protein ratios between 0.3 and 2.2 to assess their potential as imaging probes. For the first time, ctx conjugates could be achieved without showing a decrease in Φf and with an increasing labeling degree that exceeded the value of the pure dye even at a labeling degree above 2. The incorporation of hydrophilically and sterically demanding dendrimers into cyanines prevented dimer formation after covalent conjugation to the antibody. The binding functionality of the resulting ctx conjugates to the EGFR was successfully demonstrated by cell microscopy studies using EGFR expressing cell lines. In summary, the combination of hydrophilic glycerol dendrons with reactive dye labels has been established for the first time and is a promising Approach toward more powerful fluorescent labels with less dimerization. KW - Dye KW - Quantum yield KW - Fluorescence KW - Contrast agent KW - Extinction coefficient PY - 2015 DO - https://doi.org/10.1021/acs.bioconjchem.5b00097 SN - 1043-1802 VL - 26 SP - 773 EP - 781 PB - ACS Publications CY - Washington AN - OPUS4-38880 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Tan, K. H. A1 - Sattari, S. A1 - Donskyi, Ievgen A1 - Cuellar-Camacho, J. L. A1 - Cheng, C. A1 - Schwibbert, Karin A1 - Lippitz, Andreas A1 - Unger, Wolfgang A1 - Gorbushina, Anna A1 - Adeli, M. A1 - Haag, R. T1 - Functionalized 2D nanomaterials with switchable binding to investigate graphene–bacteria interactions N2 - Graphene and its derivatives have recently attracted much attention for sensing and deactivating pathogens. However, the mechanism of multivalent interactions at the graphene–pathogen interface is not fully understood. Since different physicochemical parameters of graphene play a role at this interface, control over graphene’s structure is necessary to study the mechanism of these interactions. In this work, different graphene derivatives and also zwitterionic graphene nanomaterials (ZGNMs) were synthesized with defined exposure, in terms of polymer coverage and functionality, and isoelectric points. Then, the switchable interactions of these nanomaterials with E. coli and Bacillus cereus were investigated to study the validity of the generally proposed “trapping” and “nano-knives” mechanisms for inactivating bacteria by graphene derivatives. It was found that the antibacterial activity of graphene derivatives strongly depends on the accessible area, i.e. edges and basal plane of sheets and tightness of their agglomerations. Our data clearly confirm the authenticity of “trapping” and “nano-knives” mechanisms for the antibacterial activity of graphene sheets. KW - XPS KW - Graphene KW - Graphene–bacteria interaction PY - 2018 DO - https://doi.org/10.1039/c8nr01347k SN - 2040-3364 SN - 2040-3372 VL - 10 IS - 20 SP - 9525 EP - 9537 PB - RSC CY - London AN - OPUS4-45084 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Czuban, M. A1 - Kulka, M. W. A1 - Wang, L. A1 - Koliszak, A. A1 - Achazi, K. A1 - Schlaich, C. A1 - Donskyi, Ievgen A1 - Di Luca, M. A1 - Mejia Oneto, J. M. A1 - Royzen, M. A1 - Haag, R. A1 - Trampuz, A. T1 - Titanium coating with mussel inspired polymer and bio-orthogonal chemistry enhances antimicrobial activity against Staphylococcus aureus N2 - Implant-associated infections present severe and difficult-to-treat complications after surgery, related to implant biofilm colonization. Systemic administration of antibiotics cannot reach sufficient concentrations at the infected site and may be toxic. Here we describe how mussel-inspired dendritic material coated on a titanium surface can locally activate a prodrug of daptomycin (pro-dapto) to treat methicillin-resistant Staphylococcus aureus. The mechanism of the prodrug activation is based on bio-orthogonal click chemistry between a tetrazine (Tz) and trans-cyclooctene (TCO). The former is attached to the dendritic polymer, while the later converts daptomycin into a prodrug. Characterization of the material's properties revealed that it is hydrophobic, non-toxic, and stable for a prolonged period of time. We envision that the titanium coated dendritic material will be able to improve the treatment of implant-associated infections by concentrating systemically administered antibiotic prodrugs, thus converting them into active localized medicines. KW - Bio-orthogonal chemistry KW - Antimicrobial titanium coating KW - Prodrug antibiotic KW - Antibiotic delivery KW - Antibiotic release KW - XPS PY - 2020 DO - https://doi.org/10.1016/j.msec.2020.111109 VL - 116 SP - 111109 PB - Elsevier B.V. AN - OPUS4-51204 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Donskyi, Ievgen A1 - Chen, Y. A1 - Nickl, Philip A1 - Guday, G. A1 - Qiao, H. A1 - Achasi, K. A1 - Lippitz, Andreas A1 - Unger, Wolfgang A1 - Böttcher, C. A1 - Chen, W. A1 - Adeli, M. A1 - Haag, R. T1 - Self-degrading graphene sheets for tumor therapy N2 - Low biodegradability of graphene derivatives and related health risks are the main limiting factors for their in vivo biomedical applications. Here, we present the synthesis of enzyme-functionalized graphene sheets with self-degrading properties under physiological conditions and their applications in Tumor therapy. The synergistic enzyme cascade glucose oxidase and myeloperoxidase are covalently conjugated to the surface of graphene sheets and two-dimensional (2D) platforms are obtained that can produce sodium hypochlorite from glucose. The enzyme-functionalized graphene sheets with up to 289 nm average size are degraded into small pieces (≤40 nm) by incubation under physiological conditions for 24 h. Biodegradable graphene sheets are further loaded with doxorubicin and their ability for Tumor therapy is evaluated in vitro and in vivo. The laser-triggered release of doxorubicin in combination with the enzymatic activity of the functionalized graphene sheets results in a synergistic antitumor activity. Taking advantage of their neutrophil-like activity, fast biodegradability, high photo- and chemotherapeutic effects, the novel two-dimensional nanoplatforms can be used for tumor therapeutic applications. KW - Graphene KW - Self-degrading KW - Thumor therapy KW - XPS KW - NEXAFS PY - 2020 DO - https://doi.org/10.1039/d0nr02159h SP - 1 EP - 12 PB - The Royal Society of Chemistry AN - OPUS4-50978 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Donskyi, Ievgen A1 - Azab, W. A1 - Cuellar-Camach, J.L. A1 - Guday, G. A1 - Lippitz, Andreas A1 - Unger, Wolfgang A1 - Osterrieder, K. A1 - Adeli, M. A1 - Haag, R. T1 - Functionalized nanographene sheets with high antiviral activity through synergistic electrostatic and hydrophobic interactions N2 - As resistance to traditional drugs emerges for treatment of Virus infections, the need for new methods for virus inhibition increases. Graphene derivatives with large surface areas have shown strong activity against different viruses. However, the inability of current synthetic protocols to accurately manipulate the structure of graphene sheets in order to control their antiviral activity remains a major challenge. In this work, a series of graphene derivatives with defined polyglycerol sulfate and fatty amine functionalities have been synthesized and their interactions with herpes simplex Virus type 1 (HSV-1) are investigated. While electrostatic interactions between polyglycerol sulfate and virus particles trigger the binding of graphene to virus, alkyl chains induce a high antiviral activity by secondary hydrophobic interactions. Among graphene sheets with a broad range of alkyl chains, (C3–C18), the C12-functionalized sheets showed the highest antiviral activity, indicating the optimum synergistic effect between electrostatic and hydrophobic interactions, but this derivative was toxic against the Vero cell line. In contrast, sheets functionalized with C6- and C9-alkyl chains showed low toxicity against Vero cells and a synergistic Inhibition of HSV-1. This study shows that antiviral agents against HSV-1 can be obtained by controlled and stepwise functionalization of graphene sheets and may be developed into antiviral agents for future biomedical applications. KW - Functionalized nanographene KW - X-ray Photoelectron Spectroscopy (XPS) KW - NEXAFS KW - Antiviral activity PY - 2019 DO - https://doi.org/10.1039/c9nr05273a SN - 2040-3364 VL - 11 IS - 34 SP - 15804 EP - 15809 PB - The Royal Society of Chemistry AN - OPUS4-48807 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Bawadkji, O. A1 - Cherri, M. A1 - Schäfer, A. A1 - Herziger, S. A1 - Nickl, Philip A1 - Achazi, K. A1 - Donskyi, Ievgen A1 - Adeli, M. A1 - Haag, R. T1 - One-pot covalent functionalization of 2D black phosphorus by anionic ring opening polymerization N2 - In this work, a one-pot approach for the covalent functionalization of few-layer black phosphorus (BP) by anionic ring opening polymerization of glycidol to obtain multifunctional BP-polyglycerol (BP-PG) with high amphiphilicity for near-infrared-responsive drug delivery and biocompatibility is reported. Straightforward synthesis in combination with exceptional biological and physicochemical properties designates functionalized BP-PG as a promising candidate for a broad range of biomedical applications. KW - 2D nanomaterial KW - Amphiphilicity KW - Black phosphorus KW - Hyperbranched KW - Polyglycerol KW - Water dispersibility PY - 2022 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-568833 DO - https://doi.org/10.1002/admi.202201245 SN - 2196-7350 VL - 9 SP - 1 EP - 8 PB - Wiley-VCH CY - Weinheim AN - OPUS4-56883 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Bhatia, S. A1 - Donskyi, Ievgen A1 - Block, S. A1 - Nie, C. A1 - Burdinski, A. A1 - Lauster, D. A1 - Radnik, Jörg A1 - Herrmann, A. A1 - Haag, R. A1 - Ludwig, K. A1 - Adeli, M. T1 - Wrapping and Blocking of Influenza A Viruses by Sialylated 2D Nanoplatforms N2 - Inhibition of respiratory viruses is one of the most urgent topics as underlined by different pandemics in the last two decades. This impels the development of new materials for binding and incapacitation of the viruses. In this work, we have demonstrated that an optimal deployment of influenza A virus (IAV) targeting ligand sialic acid (SA) on a flexible 2D platform enables its binding and wrapping around IAV particles. A series of 2D sialylated platforms consisting graphene and polyglycerol are prepared with different degrees of SA functionalization around 10%, 30%, and 90% named as G-PG-SAL, G-PG-SAM, and G-PG-SAH, respectively. The cryo-electron tomography (Cryo-ET) analysis has proved wrapping of IAV particles by G-PG-SAM. A confocal-based colocalization assay established for these materials has offered the comparison of binding potential of sialylated and non-sialylated nanoplatforms for IAV. With this method, we have estimated the binding potential of the G-PG-SAM and G-PG-SAH sheets for IAV particles around 50 and 20 times higher than the control sheets, respectively, whereas the low functionalized G-PG-SAL have not shown any significant colocalization value. Moreover, optimized G-PG-SAM exhibits high potency to block IAV from binding with the MDCK cells. KW - 2D Materials KW - Graphhene KW - Influenza A virus KW - Sialic acid KW - wrapping PY - 2021 DO - https://doi.org/10.1002/admi.202100285 VL - 8 IS - 12 SP - 285 PB - Wiley VCH AN - OPUS4-52715 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Nickl, Philip A1 - Hilal, T. A1 - Olal, D. A1 - Donskyi, Ievgen A1 - Radnik, Jörg A1 - Ludwig, K. A1 - Haag, R. T1 - A New Support Film for Cryo Electron Microscopy Protein Structure Analysis Based on Covalently Functionalized Graphene N2 - Protein adsorption at the air–water interface is a serious problem in cryogenic electron microscopy (cryoEM) as it restricts particle orientations in the vitrified ice-film and promotes protein denaturation. To address this issue, the preparation of a graphene-based modified support film for coverage of conventional holey carbon transmission electron microscopy (TEM) grids is presented. The chemical modification of graphene sheets enables the universal covalent anchoring of unmodified proteins via inherent surface-exposed lysine or cysteine residues in a one-step reaction. Langmuir–Blodgett (LB) trough approach is applied for deposition of functionalized graphene sheets onto commercially available holey carbon TEM grids. The application of the modified TEM grids in single particle analysis (SPA) shows high protein binding to the surface of the graphene-based support film. Suitability for high resolution structure determination is confirmed by SPA of apoferritin. Prevention of protein denaturation at the air–water interface and improvement of particle orientations is shown using human 20S proteasome, demonstrating the potential of the support film for structural biology. KW - Functionalized graphene KW - Transmission electron microsocpy KW - Protein structure PY - 2022 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-566443 DO - https://doi.org/10.1002/smll.202205932 SN - 1613-6810 SP - 2205932 PB - Wiley VCH AN - OPUS4-56644 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -