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
KA910	Shell-sheddable dendritic polyglycerol sulfates loaded with sunitinib for inhibition of tumor angiogenesis			"Koeppe, H.; Horn, D.; Scholz, J.; Quaas, E.; Schotz, S.; Reisbeck, F.; Achazi, K.; Mohammadifar, E.; Dernedde, J.; Haag, R."		Int J Pharm			2023	7	25	"*Endothelial Cells; *Sulfates; Angiogenesis; Anti-cancer drugs; Cell Line, Tumor; Core-shell; Glycerol; HeLa Cells; Humans; Nanocarrier; Polyglycerol; Polymers/chemistry; Sunitinib"				https://doi.org/10.1016/j.ijpharm.2023.123158		journalArticle		1873-3476 (Electronic) 0378-5173 (Linking)				Induced angiogenesis, a specific hallmark of cancer, plays a vital role in tumor progression and can be targeted by inhibitors like sunitinib. Sunitinib is a small hydrophobic molecule suffering from low bioavailability and a short half-life in the bloodstream. To overcome these drawbacks, suitable drug delivery systems need to be developed. In this work dendritic polyglycerol (dPG), a well-known polymer, was functionalized with a sheddable shell. Therefore, aliphatic chains of different lengths (C(5), C(9), C(11)) were coupled to dPG through a cleavable ester bond. To restore water solubility and improve tumor targeting, the surface was decorated with sulfate groups. The resulting shell-sheddable dPG sulfates were characterized and evaluated regarding their loading capacity and biocompatibility in cell culture. The nine-carbon chain derivative (dPG-TNS) was selected as the best candidate for further experiments due to its high drug loading capacity (20 wt%), and a sustained release in vitro. The cellular biocompatibility of the blank carrier up to 1 mg/mL was confirmed after 24 h incubation on HeLa cells. Furthermore, the shell-cleavability of dPG-TNS under different physiological conditions was shown in a degradation study over four weeks. The activity of sunitinib-loaded dPG-TNS was demonstrated in a tube formation assay on Human umbilical vein endothelial cells (HUVECs). Our results suggest that the drug-loaded nanocarrier is a promising candidate to be further investigated in tumor treatments, as it shows similar efficacy to free sunitinib while overcoming its limitations.				
KA911	Bromo- and glycosyl-substituted BODIPYs for application in photodynamic therapy and imaging			"Hohlfeld, B. F.; Steen, D.; Wieland, G. D.; Achazi, K.; Kulak, N.; Haag, R.; Wiehe, A."		Org Biomol Chem			2023	4	12	"*Photochemotherapy; *Photosensitizing Agents/chemistry; Boron Compounds/chemistry; Cell Line"				https://doi.org/10.1039/d2ob02174a		journalArticle		1477-0539 (Electronic) 1477-0520 (Linking)				The introduction of heavy atoms into the BODIPY-core structure has proven to be a straightforward strategy for optimizing the design of such dyes towards enhanced generation of singlet oxygen rendering them suitable as photosensitizers for photodynamic therapy (PDT). In this work, BODIPYs are presented by combining the concept of bromination with nucleophilic aromatic substitution (S(N)Ar) of a pentafluorophenyl or a 4-fluoro-3-nitrophenyl moiety to introduce functional groups, thus improving the phototoxic effect of the BODIPYs as well as their solubility in the biological environment. The nucleophilic substitution enabled functionalization with various amines and alcohols as well as unprotected thiocarbohydrates. The phototoxic activity of these more than 50 BODIPYs has been assessed in cellular assays against four cancer cell lines in order to more broadly evaluate their PDT potential, thus accounting for the known variability between cell lines with respect to PDT activity. In these investigations, dibrominated polar-substituted BODIPYs, particularly dibrominated glyco-substituted compounds, showed promising potential as photomedicine candidates. Furthermore, the cellular uptake of the glycosylated BODIPYs has been confirmed via fluorescence microscopy.				
KA912	Synthesis and Comparison of Linear Polymannosides for Direct Binding with			"Hanheiser, N.; Parshad, B.; Povolotsky, T. L.; Khatri, V.; Achazi, K.; Bhatia, S."		Macromolecular Chemistry and Physics			2023	12		"adhesion; adhesion inhibition; escherichia coli; glycopolymers; infection; inhibition; microscale thermophoresis; multivalent presentation; poly(man alpha 1,2man); polyglycerol; polyman"				https://doi.org/10.1002/macp.202300339		journalArticle		1022-1352				Here, the synthesis of linear polyglycerols bearing multiple copies of mono and dimannosides (LPG(40)Man(0.60) and LPG(40)(Man alpha 1,2Man)(0.60)) is demonstrated. A method based on label-free microscale thermophoresis is optimized to determine the direct binding affinity of multivalent mannosides for Escherichia coli (E. coli) strain ORN178 that produces the fimbriae protein FimH. It is observed that the LPG(40)(Man alpha 1,2Man)(0.60) exhibits only a modest onefold improvement in binding as compared to LPG(40)Man(0.60). Nevertheless, both the multivalent mannosides display remarkably very low nm binding constant (K-d) in contrast to the high mu m K-d of the single alpha-d-methylmannoside for intact E. coli ORN178 particles. Furthermore, in an adhesion-inhibition assay, both multivalent mannosides show 50% inhibition of bacteria adhesion to the HT-29 colon cells at low mu m concentrations.				
KA913	Fluorinated dendritic amphiphiles, their stomatosome aggregates and application in enzyme encapsulation			"Guitton-Spassky, T.; Junge, F.; Singh, A. K.; Schade, B.; Achazi, K.; Maglione, M.; Sigrist, S.; Rashmi, R.; Haag, R."		Nanoscale			2023	5	4	"*Enzymes, Immobilized; *Urease; Microscopy, Electron, Transmission"				https://doi.org/10.1039/d3nr00493g		journalArticle		2040-3372 (Electronic) 2040-3364 (Linking)				"Enzymes are more selective and efficient than synthetic catalysts but are limited by difficult recycling. This is overcome by immobilisation, namely through encapsulation, with the main drawback of this method being slow diffusion of products and reactants, resulting in effectively lowered enzyme activity. Fluorinated dendritic amphiphiles were reported to self-assemble into regularly perforated bilayer vesicles, so-called ""stomatosomes"". It was proposed that they could be promising novel reaction vessels due to their increased porosity while retaining larger biomolecules at the same time. Amphiphiles were synthesised and their aggregation was analysed by cryogenic transmission electron microscopy (cryo-TEM) and dynamic light scattering (DLS) in buffered conditions necessary for enzyme encapsulation. Urease and albumin were encapsulated using the thin-film hydration method and investigated by confocal and time-gated stimulated emission depletion microscopy (gSTED). Their release was then used to probe the selective retention of cargo by stomatosomes. Free and encapsulated enzyme activity were compared and their capacity to be reused was evaluated using the Berthelot method. Urease was successfully encapsulated, did not leak out at room temperature, and showed better activity in perforated vesicles than in closed vesicles without perforations. Encapsulated enzyme could be reused with retained activity over 8 cycles using centrifugation, while free enzyme had to be filtrated. These results show that stomatosomes may be used in enzyme immobilisation applications and present advantages over closed vesicles or free enzyme."				
KA914	Benzoxaborole-grafted high molecular weight chitosan from prawn: Synthesis, characterization, target recognition and antibacterial properties			"Garcia Cambon, T. A.; Lopez, C. S.; Hanheiser, N.; Bhatia, S.; Achazi, K.; Rivas, M. V.; Spagnuolo, C. C."		Carbohydr Polym			2023	9	15	"*Chitosan/chemistry; Anti-Bacterial Agents/chemistry; Benzoxaborole; Boronic acid; Chitosan; Covalent dynamic interaction; Molecular Weight; Polymers/chemistry; Spectroscopy, Fourier Transform Infrared"				https://doi.org/10.1016/j.carbpol.2023.120925		journalArticle		1879-1344 (Electronic) 0144-8617 (Linking)				Boronated polymers are in the focus of dynamic functional materials due to the versatility of the B-O interactions and accessibility of precursors. Polysaccharides are highly biocompatible, and therefore, an attractive platform for anchoring boronic acid groups for further bioconjugation of cis-diol containing molecules. We report for the first time the introduction of benzoxaborole by amidation of the amino groups of chitosan improving solubility and introducing cis-diol recognition at physiological pH. The chemical structures and physical properties of the novel chitosan-benzoxaborole (CS-Bx) as well as two phenylboronic derivatives synthesized for comparison, were characterized by nuclear magnetic resonance (NMR), infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), dynamic light scattering (DLS), rheology and optical spectroscopic methods. The novel benzoxaborole grafted chitosan was perfectly solubilized in an aqueous buffer at physiological pH, extending the possibilities of boronated materials derived from polysaccharides. The dynamic covalent interaction between boronated chitosan and model affinity ligands, was studied by means of spectroscopy methods. A glycopolymer derived from poly(isobutylene-alt-anhydride) was also synthesized to study the formation of dynamic assemblies with benzoxaborole-grafted chitosan. A first approximation to apply fluorescence microscale thermophoresis for the interactions of the modified polysaccharide is also discussed. Additionally, the activity of CSBx against bacterial adhesion was studied.				
KA915	Dendritic polyglycerolsulfate-SS-poly(ester amide) micelles for the systemic delivery of docetaxel: pushing the limits of stability through the insertion of pi-pi interactions			"Braatz, D.; Peter, J. H.; Dimde, M.; Quaas, E.; Ludwig, K.; Achazi, K.; Schirner, M.; Ballauff, M.; Haag, R."		Journal of Materials Chemistry B			2023	5	3	"formulation; paclitaxel; polymeric micelles; solid-state nmr; tool"				https://doi.org/10.1039/d3tb00055a		journalArticle		2050-750x				Insufficient stability of micellar drug delivery systems is still the major limitation to their systematic application in chemotherapy. This work demonstrates novel pi-electron stabilized polyelectrolyte block copolymer micelles based on dendritic polyglycerolsulfate-cystamine-block-poly(4-benzoyl-1,4-oxazepan-7-one)-pyrene (dPGS-SS-POxPPh-Py) presenting a very low critical micelle concentration (CMC) of 0.3 mg L-1 (18 nM), 55-fold lower than that of conventional amphiphilic block copolymer micelles. The drug loading capacities of up to 13 wt% allow the efficient encapsulation of the chemotherapeutic Docetaxel (DTX). The spherical morphology of the micelles was proven by cryogenic electron microscopy (cryo-EM). Gaussian Analysis revealed well-defined sizes of 57 nm and 80 nm in the unloaded/loaded state, respectively. Experiments by dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-VIS), fluorescence spectroscopy, and cross-polarization solid-state C-13 NMR studied the pi-pi interactions between the core-forming block segment of dPGS-SS-POxPPh-Py and DTX. The findings point to a substantial contribution of these noncovalent interactions to the system's high stability. By confocal laser scanning microscopy (CLSM), the cellular uptake of fluorescein-labelled FITC-dPGS-SS-POxPPh-Py micelles was monitored after one day displaying the successful cell insertion of the cargo-loaded systems. To ensure the drug release in cancerous cells, the disassembly of the micellar DTX-formulations was achieved by reductive and enzymatic degradation studied by light scattering and GPC experiments. Further, no size increase nor disassembly in the presence of human serum proteins after four days was detected. The precise in vitro drug release was also given by the high potency of inhibiting cancer cell growth, finding half-maximal inhibitory concentrations (IC50) efficiently reduced to 68 nM coming along with high viabilities of the empty polymer materials tested on tumor-derived HeLa, A549, and McF-7 cell lines after two days. This study highlights the substantial potential of micelles tailored through the combination of pi-electron stabilization with dendritic polyglycerolsulfate for targeted drug delivery systems, enabling them to have a significant foothold in the clinical treatment of cancer.				
KA916	Mucin-Inspired Single-Chain Polymer (MIP) Fibers as Potent SARS-CoV-2 Inhibitors			"Bej, R.; Nie, C.; Ludwig, K.; Ahmadi, V.; Trimpert, J.; Adler, J. M.; Povolotsky, T. L.; Achazi, K.; Kagelmacher, M.; Vidal, R. M.; Dernedde, J.; Kaufer, B. B.; Haag, R."		Angew Chem Int Ed Engl			2023	7	17	"*covid-19; *Molecular Imprinting/methods; Biocompatibility; Humans; Mucin-Inspired Polymer; Mucins; Polymers/pharmacology/chemistry; RAFT Polymerization; SARS-CoV-2; SARS-Cov-2 Inhibition; Single-Chain Fiber"				https://doi.org/10.1002/anie.202304010		journalArticle		1521-3773 (Electronic) 1433-7851 (Linking)				Mucins are the key component of the defensive mucus barrier. They are extended fibers of very high molecular weight with diverse biological functions depending strongly on their specific structural parameters. Here, we present a mucin-inspired nanostructure, produced via a synthetic methodology to prepare methacrylate-based dendronized polysulfates (MIP-1) on a multi gram-scale with high molecular weight (MW=450 kDa) and thiol end-functionalized mucin-inspired polymer (MIP) via RAFT polymerization. Cryo-electron tomography (Cryo-ET) analysis of MIP-1 confirmed a mucin-mimetic wormlike single-chain fiber structure (length=144+/-59 nm) in aqueous solution. This biocompatible fiber showed promising activity against SARS-CoV-2 and its mutant strain, with a remarkable low half maximal (IC(50) ) inhibitory concentration (IC(50) =10.0 nM). Additionally, we investigate the impact of fiber length on SARS-CoV-2 inhibition by testing other functional polymers (MIPs) of varying fiber lengths.				
KA917	Evaluation of Transport Potential of Alkylated and Fluoroalkylated Amphiphilic Hybrid Nanoarchitectures			"Verma, D.; Rashmi; Rathore, D.; Achazi, K.; Schade, B.; Haag, R.; Sharma, S. K."		Acs Applied Polymer Materials			2022	10	10	"behavior; dendrimer; drug-delivery; enzymatic release; fluorinated amphiphiles; fluoroalkylated amphiphile; guest encapsulation; membrane; nanocarriers; self-assembly; soft"				https://doi.org/10.1021/acsapm.2c01176		journalArticle		2637-6105				The unique segregation and self-assembly properties of fluorinated amphiphiles into supramolecular architectures have attracted substantial attention in recent years. In this study, we report the design and synthesis of six newer hybrid nonionic amphiphiles with hydrophobic alkyl/fluoroalkyl chains and hydrophilic polyethylene glycol (PEG) units of different lengths and evaluate and compare their drug delivery applications. On the hydrophobic side, the amphiphiles differ in having either two alkyl chains, two fluoroalkyl chains, or one alkyl and one fluoroalkyl chain. This allowed for a systematic comparison of the physicochemical and transport abilities. The aggregation phenomenon of the amphiphiles was monitored with Cryo-TEM. Cytotoxicity and cellular uptake studies were performed to evaluate the pharmacological potential. Candida antarctica lipase (Novozym-435) immobilized on solid support was used to facilitate the release of the encapsulated cargo. Our study highlights the potential and properties of the fluoroalkyl-based nanocarriers.				
KA918	Polyanionic Amphiphilic Dendritic Polyglycerols as Broad-Spectrum Viral Inhibitors with a Virucidal Mechanism			"Mohammadifar, E.; Gasbarri, M.; Cagno, V.; Achazi, K.; Tapparel, C.; Haag, R.; Stellacci, F."		Biomacromolecules			2022	3	14	"*Metal Nanoparticles; *Viruses; Anticoagulants/pharmacology; Antiviral Agents/chemistry/pharmacology; Glycerol; Gold; Heparin/pharmacology; Polymers/pharmacology"				https://doi.org/10.1021/acs.biomac.1c01376		journalArticle		1526-4602 (Electronic) 1525-7797 (Linking)				"Heparin has been known to be a broad-spectrum inhibitor of viral infection for almost 70 years, and it has been used as a medication for almost 90 years due to its anticoagulant effect. This nontoxic biocompatible polymer efficiently binds to many types of viruses and prevents their attachment to cell membranes. However, the anticoagulant properties are limiting their use as an antiviral drug. Many heparin-like compounds have been developed throughout the years; however, the reversible nature of the virus inhibition mechanism has prevented their translation to the clinics. In vivo, such a mechanism requires the unrealistic maintenance of the concentration above the binding constant. Recently, we have shown that the addition of long hydrophobic linkers to heparin-like compounds renders the interaction irreversible while maintaining the low-toxicity and broad-spectrum activity. To date, such hydrophobic linkers have been used to create heparin-like gold nanoparticles and beta-cyclodextrins. The former achieves a nanomolar inhibition concentration on a non-biodegradable scaffold. The latter, on a fully biodegradable scaffold, shows only a micromolar inhibition concentration. Here, we report that the addition of hydrophobic linkers to a new type of multifunctional scaffold (dendritic polyglycerol, dPG) creates biocompatible compounds endowed with nanomolar activity. Furthermore, we present an in-depth analysis of the molecular design rules needed to achieve irreversible virus inhibition. The most active compound (dPG-5) showed nanomolar activity against herpes simplex virus 2 (HSV-2) and respiratory syncytial virus (RSV), giving a proof-of-principle for broad-spectrum while keeping low-toxicity. In addition, we demonstrate that the virucidal activity leads to the release of viral DNA upon the interaction between the virus and our polyanionic dendritic polymers. We believe that this paper will be a stepping stone toward the design of a new class of irreversible nontoxic broad-spectrum antivirals."				
KA919	Fabrication of hydrolase responsive diglycerol based Gemini amphiphiles for dermal drug delivery applications			"Mittal, A.; Krishna; Zabihi, F.; Rancan, F.; Achazi, K.; Nie, C.; Vogt, A.; Haag, R.; Sharma, S. K."		Rsc Advances			2022	8	16	"behavior; curcumin; nanocarriers; nanoparticles; nanostructures; penetration; spacer; supra-amphiphiles; surfactants"				https://doi.org/10.1039/d2ra03090j		journalArticle		2046-2069 (Electronic) 2046-2069 (Linking)				Since biocatalysts manoeuvre most of the physiological activities in living organisms and exhibit extreme selectivity and specificity, their use to trigger physicochemical change in polymeric architectures has been successfully used for targeted drug delivery. Our major interest is to develop lipase responsive nanoscale delivery systems from bio-compatible and biodegradable building blocks. Herein, we report the synthesis of four novel non-ionic Gemini amphiphiles using a chemo-enzymatic approach. A symmetrical diglycerol has been used as a core that is functionalised with alkyl chains for the creation of a hydrophobic cavity, and for aqueous solubility (polyethylene glycol) monomethyl ether (mPEG) is incorporated. Such systems can exhibit a varied self-assembly behaviour leading to the observance of different morphological structures. The aggregation behaviour of the synthesised nanocarrier was studied by dynamic light scattering (DLS) and critical aggregation concentration (CAC) measurements. The nanotransport potential of amphiphiles was investigated for hydrophobic guest molecules, i.e. Nile red, nimodipine and curcumin. Cytotoxicity of the amphiphiles was studied using HeLa and MCF7 cell lines at different concentrations, i.e. 0.05, 0.1, and 0.5 mg mL(-1). All nanocarriers were found to be non-cytotoxic up to a concentration of 0.1 mg mL(-1). Confocal laser scanning microscopy (cLSM) study suggested the uptake of encapsulated dye in the cytosol of the cancer cells within 4 h, thus implying that amphiphilic systems can efficiently transport hydrophobic drug molecules into cells. The biomedical application of the synthesised Gemini amphiphiles was also investigated for dermal drug delivery. In addition, the enzyme-mediated release study was performed that demonstrated 90% of the dye is released within three days. All these results supported the capability of nanocarriers in drug delivery systems.