name title fuMetaTitel body fuDCcreator fuDCcreatorLinks fuDCpublisher fuDCpublisherLocation fuDCSizeOrDuration fuDCdateYear fuDCdateMonth fuDCdateDay fuDCsubject fuDCrelationPartOf fuDCrelation fuDClanguage fuDCsource fuDCcontributor fuDCtype fuDCformat fuDCidentifier fuDCcoverage fuDCrights fuDCdescriptionDE fuDCdescriptionEN fuDCIdentifierBibliographicCitation fuBild fuDCBibtex fuLinksZumThema KA920 Hydroquinone-functionalized cyanine dye as reduction-sensitive probe for imaging of biological reducing species "Heing-Becker, I.; Achazi, K.; Haag, R.; Licha, K." Dyes and Pigments 2022 5 "biothiols; cyanines; discrimination; fluorescent dyes; fluorescent-probes; glutathione; in-vivo; quinone; reduction-sensitive; selective detection; thiols" https://doi.org/10.1016/j.dyepig.2022.110198 journalArticle 0143-7208 "The redox chemistry and status of different cell types and tissues has still not been well understood and thus represents a major focus for the development of novel responsive fluorophores. In this context, there is ongoing search for reduction-sensitive probes that can globally or specifically image reducing environments species in biological settings. Here, the synthesis and characterization of responsive cyanine dyes operating in the near-infrared (NIR) is reported based on the use of the hydroquinone/quinone and catechol/quinone couple. The introduction of a hydroquinone group into the meso-position of an indodicarbocyanine dye via a Suzuki cross coupling reaction created a water-soluble fluorescent ""on-off-on "" probe whose fluorescence can be modulated through oxidation and reduction. By adding biologically relevant reducing species, such as glutathione, cysteine or ascorbate, the ""off ""-probe could be rapidly turned on around 660 nm within 30 s. Reversible switching tween the ""on "" and ""off "" form was demonstrated. Furthermore, the sensor was applied in confocal microscopy studies as a reduction-sensitive probe for bioimaging in living cells." KA921 Polylactide-Block-Polyglycerol-Functionalized Black Phosphorous Nanosheets for Tumor Therapy "Donskyi, I. S.; Huang, X.; Wichmann, N.; Bawadkji, O.; Ahmed, R.; Nickl, P.; Herziger, S.; Radnik, J.; Achazi, K.; Qiao, H. S.; Adeli, M." Acs Applied Nano Materials 2022 9 23 "air; black phosphorus; covalent functionalization; efficacy; hyperbranched polyglycerol; nanomaterials; nanoparticles; one-pot; photothermal therapy; ring-opening polymerization; transition; tumor therapy; two-dimensional materials" https://doi.org/10.1021/acsanm.2c03093 journalArticle 2574-0970 2574-0970 Here, we report a one-pot, straightforward, and efficient method for the covalent functionalization of black phosphorous (BP) nanosheets with biopolymers on a gram scale. L-lactide and glycidol monomers were stepwise copolymerized onto the surface of exfoliated BP resulting in highly water-soluble functional nanosheets (BP-PLA-PG). In contrast to pristine BP, their functionalized counterparts did not degrade under ambient conditions and were stable for several weeks. Owing to their stability, efficient photothermal effect, and low toxicity, BP-PLA-PG sheets were loaded with doxorubicin (DOX), and their anticancer effect was investigated in vitro and in vivo. The laser-triggered release of DOX, in combination with the photothermal effect of the functionalized BP sheets, manifested in strong antitumor effects in animal studies. One-pot straightforward functionalization, high loading capacity, low toxicity, excellent water dispersibility and stability, as well as high functionality, support BP-PLA-PG as a promising vector for the future biomedical applications, including targeted drug delivery and bioimaging. KA922 One-Pot Covalent Functionalization of 2D Black Phosphorus by Anionic Ring Opening Polymerization "Bawadkji, O.; Cherri, M.; Schaefer, A.; Herziger, S.; Nickl, P.; Achazi, K.; Donskyi, I. S.; Adeli, M.; Haag, R." Advanced Materials Interfaces 2022 11 "2d nanomaterials; amphiphilicity; biological evaluation; black phosphorus; hyperbranched polyglycerol; hyperbranched polyglycerols; nanomaterials; nanoparticles; nanosheets; passivation; photothermal therapy; platform; stability; surface; water dispersibility" https://doi.org/10.1002/admi.202201245 journalArticle 2196-7350 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. KA923 Graphene-Based Bacterial Filtration via Electrostatic Adsorption "Ahmed, R.; Vaishampayan, A.; Achazi, K.; Grohmann, E.; Haag, R.; Wagner, O." Advanced Materials Interfaces 2022 2 "chemistry; dendrimers; filters; flow rate; graphene oxide; membranes; outbreaks; oxide; polycationic microsheets; water; water filter; water purification" https://doi.org/10.1002/admi.202101917 journalArticle 2196-7350 Flexible graphene oxide (GO) microsheets with attached positively charged polymers, termed GOX microsheets, are efficient at bacterial adsorption, as they bind electrostatically to bacterial membranes' negative surface charge. The authors explore an antimicrobial water filter application for GOX's extremely high surface area and its previously described efficient bacterial adsorption.Cellulose-fiber carrier material is functionalized with GOX microsheets to create an adsorption-based bacteria filtration material. The morphology and charge density (7.8 x 10(19) g(-1)) of the prepared GOX fibers are determined by scanning electron microscopy and dye adsorption assay, and widefield fluorescence microscopy is used to visualize the adsorption of stained Escherichia coli bacterial cells on the fibers. GOX fibers are tested in filtration setups to investigate their bacteria removal performance. The experimental results, with 100 mg of GOX fibers filtering 2.4 x 10(9) colony-forming units (CFU) from an E. coli bacterial culture with 99.5% bacterial reduction, demonstrate the fibers' high bacteria loading capacity. The electrostatic adsorption-based filtration mechanism allows the filter to be operated at higher flow rates than micropore membrane filters, while maintaining 3-log bacterial reduction. GOX filter materials removing bacteria via adsorption are a high flow rate alternative to current water filtration processes that rely on size-exclusion. KA924 Tunable Polyglycerol-Based Redox-Responsive Nanogels for Efficient Cytochrome C Delivery "Schotz, S.; Reisbeck, F.; Schmitt, A. C.; Dimde, M.; Quaas, E.; Achazi, K.; Haag, R." Pharmaceutics 2021 8 17 "iEDDA; nanogels; protein delivery" https://doi.org/10.3390/pharmaceutics13081276 journalArticle 1999-4923 (Print) 1999-4923 (Electronic) 1999-4923 (Linking) The sensitivity of therapeutic proteins is a challenge for their use in biomedical applications, as they are prone to degradation and opsonization, thus limiting their potential. This demands for the development of drug delivery systems shielding proteins and releasing them at the site of action. Here, we describe the synthesis of novel polyglycerol-based redox-responsive nanogels and report on their potential as nanocarrier systems for the delivery of cytochrome C (CC). This system is based on an encapsulation protocol of the therapeutic protein into the polymer network. NGs were formed via inverse nanoprecipitation using inverse electron-demand Diels-Alder cyclizations (iEDDA) between methyl tetrazines and norbornenes. Coprecipitation of CC led to high encapsulation efficiencies. Applying physiological reductive conditions of l-glutathione (GSH) led to degradation of the nanogel network, releasing 80% of the loaded CC within 48 h while maintaining protein functionality. Cytotoxicity measurements revealed high potency of CC-loaded NGs for various cancer cell lines with low IC(50) values (up to 30 mug.mL(-1)), whereas free polymer was well tolerated up to a concentration of 1.50 mg.mL(-1). Confocal laser scanning microscopy (CLSM) was used to monitor internalization of free and CC-loaded NGs and demonstrate the protein cargo's release into the cytosol. KA925 Gram Scale Synthesis of Dual-Responsive Dendritic Polyglycerol Sulfate as Drug Delivery System "Reisbeck, F.; Ozimkovski, A.; Cherri, M.; Dimde, M.; Quaas, E.; Mohammadifar, E.; Achazi, K.; Haag, R." Polymers (Basel) 2021 3 23 "dendritic polyglycerol sulfates; drug delivery system; dual-responsiveness" https://doi.org/10.3390/polym13060982 journalArticle 2073-4360 (Electronic) 2073-4360 (Linking) Biocompatible polymers with the ability to load and release a cargo at the site of action in a smart response to stimuli have attracted great attention in the field of drug delivery and cancer therapy. In this work, we synthesize a dual-responsive dendritic polyglycerol sulfate (DR-dPGS) drug delivery system by copolymerization of glycidol, epsilon-caprolactone and an epoxide monomer bearing a disulfide bond (SSG), followed by sulfation of terminal hydroxyl groups of the copolymer. The effect of different catalysts, including Lewis acids and organic bases, on the molecular weight, monomer content and polymer structure was investigated. The degradation of the polymer backbone was proven in presence of reducing agents and candida antarctica Lipase B (CALB) enzyme, which results in the cleavage of the disulfides and ester bonds, respectively. The hydrophobic anticancer drug Doxorubicin (DOX) was loaded in the polymer and the kinetic assessment showed an enhanced drug release with glutathione (GSH) or CALB as compared to controls and a synergistic effect of a combination of both stimuli. Cell uptake was studied by using confocal laser scanning microscopy with HeLa cells and showed the uptake of the Dox-loaded carriers and the release of the drug into the nucleus. Cytotoxicity tests with three different cancer cell lines showed good tolerability of the polymers of as high concentrations as 1 mg mL(-1)(,) while cancer cell growth was efficiently inhibited by DR-dPGS@Dox. KA926 "Correction to ""Inhibition of Herpes Simplex Virus Type 1 Attachment and Infection by Sulfated Polyglycerols with Different Architectures""" "Pouyan, P.; Nie, C.; Bhatia, S.; Wedepohl, S.; Achazi, K.; Osterrieder, N.; Haag, R." Biomacromolecules 2021 5 10 https://doi.org/10.1021/acs.biomac.1c00483 journalArticle 1526-4602 (Electronic) 1525-7797 (Linking) KA927 Inhibition of Herpes Simplex Virus Type 1 Attachment and Infection by Sulfated Polyglycerols with Different Architectures "Pouyan, P.; Nie, C.; Bhatia, S.; Wedepohl, S.; Achazi, K.; Osterrieder, N.; Haag, R." Biomacromolecules 2021 4 12 "*Herpesvirus 1, Human; Antiviral Agents/pharmacology; Glycerol; Polymers; Sulfates" https://doi.org/10.1021/acs.biomac.0c01789 journalArticle 1526-4602 (Electronic) 1525-7797 (Linking) Inhibition of herpes simplex virus type 1 (HSV-1) binding to the host cell surface by highly sulfated architectures is among the promising strategies to prevent virus entry and infection. However, the structural flexibility of multivalent inhibitors plays a major role in effective blockage and inhibition of virus receptors. In this study, we demonstrate the inhibitory effect of a polymer scaffold on the HSV-1 infection by using highly sulfated polyglycerols with different architectures (linear, dendronized, and hyperbranched). IC(50) values for all synthesized sulfated polyglycerols and the natural sulfated polymer heparin were determined using plaque reduction infection assays. Interestingly, an increase in the IC(50) value from 0.03 to 374 nM from highly flexible linear polyglycerol sulfate (LPGS) to less flexible scaffolds, namely, dendronized polyglycerol sulfate and hyperbranched polyglycerol sulfate was observed. The most potent LPGS inhibits HSV-1 infection 295 times more efficiently than heparin, and we show that LPGS has a much reduced anticoagulant capacity when compared to heparin as evidenced by measuring the activated partial thromboplastin time. Furthermore, prevention of infection by LPGS and the commercially available drug acyclovir were compared. All tested sulfated polymers do not show any cytotoxicity at concentrations of up to 1 mg/mL in different cell lines. We conclude from our results that more flexible polyglycerol sulfates are superior to less flexible sulfated polymers with respect to inhibition of HSV-1 infection and may constitute an alternative to the current antiviral treatments of this ubiquitous pathogen. KA928 Newer Non-ionic A(2) B(2) -Type Enzyme-Responsive Amphiphiles for Drug Delivery "Krishna; Parshad, B.; Achazi, K.; Bottcher, C.; Haag, R.; Sharma, S. K." ChemMedChem 2021 5 6 "A549 Cells; amphiphiles; Cell Survival/drug effects; cellular uptake; controlled release; Drug Carriers/*chemistry/pharmacology; drug delivery; Fungal Proteins/metabolism; Humans; Hydrolysis; Hydrophobic and Hydrophilic Interactions; Lipase/metabolism; Microscopy, Confocal; Microscopy, Electron, Transmission; nanostructures; Nanostructures/chemistry; Nimodipine/chemistry/metabolism; Oxazines/chemistry; Polyethylene Glycols/chemistry; self-assembly" https://doi.org/10.1002/cmdc.202100031 journalArticle 1860-7187 (Electronic) 1860-7179 (Linking) A new series of nonionic gemini amphiphiles have been synthesized in a multi-step chemoenzymatic approach by using a novel A(2) B(2) -type central core consisting of conjugating glycerol and propargyl bromide on 5-hydroxy isophthalic acid. A pair of hydrophilic monomethoxy poly(ethylene glycol) (mPEG) and hydrophobic linear alkyl chains (C(12) /C(15) ) were then added to the core to obtain amphiphilic architectures. The aggregation tendency in aqueous media was studied by dynamic light scattering, fluorescence spectroscopy and cryogenic transmission electron microscopy. The nanotransport potential of the amphiphiles was studied for model hydrophobic guests, that is, the dye Nile Red and the drug Nimodipine by using UV/Vis and fluorescence spectroscopy. Evaluation of the viability of amphiphile-treated A549 cells showed them to be well tolerated up to the concentrations studied. Being ester based, these amphiphiles exhibit stimuli-responsive sensitivity towards esterases, and a rupture of amphiphilic architecture was observed in the presence of immobilized Candida antarctica lipase (Novozym 435), thus facilitating release of the encapsulated guest from the aggregate. KA929 Graphene Sheets with Defined Dual Functionalities for the Strong SARS-CoV-2 Interactions "Donskyi, I. S.; Nie, C.; Ludwig, K.; Trimpert, J.; Ahmed, R.; Quaas, E.; Achazi, K.; Radnik, J.; Adeli, M.; Haag, R.; Osterrieder, K." Small 2021 3 "Antiviral Agents/pharmacology; COVID-19/epidemiology/virology; Cryoelectron Microscopy; graphene; graphene-based polyglycerol sulfates; Graphite/*chemistry; Humans; Microscopy, Atomic Force; Pandemics; SARS-CoV-2 inhibitor; SARS-CoV-2/*chemistry/drug effects; virucidality" https://doi.org/10.1002/smll.202007091 journalArticle 1613-6829 (Electronic) 1613-6810 (Print) 1613-6810 (Linking) 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 (SARS-CoV-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.