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
KA950	Chemo-enzymatic synthesis of dendronized polymers for cyanine dye encapsulation			"Kumar, S.; Achazi, K.; Licha, K.; Manchanda, P.; Haag, R.; Sharma, S. K."		Advances in Polymer Technology			2018	10		"azidotriglycerol; cyanine 3; cytotoxicity; drug-delivery; indocyanine-green; nanoparticles; peg; photophysics; stability; systems; transport capacity"				https://doi.org/10.1002/adv.21839		journalArticle		0730-6679				Cyanine 3 is an amphiphilic fluorescent dye used in optical imaging, bioengineering, and for cellular internalization. However, the applications of the dye are limited due to its poor aqueous stability, aggregation tendency, and lack of selectivity. To address these issues, we have developed PEG and azidotriglycerol based dendronized polymers using Novozym 435 as a biocatalyst under solvent free conditions. The resulting polymer having azido and hydroxyl functionalities available in the backbone were further grafted with alkyl chains and polyglycerol dendrons using esterification and 'Click' chemistry approach. These polymers form stable micelles at micromolar concentration. All the polymers were characterized from their spectral data and their tendency to encapsulate cyanine 3 dye studied using UV-Vis and fluorescence spectroscopy. The cytotoxicity study of the polymers performed against A549 cell lines suggests them to be nontoxic up to a concentration of 500 mu g/ml.				
KA951	Droplet-Based Microfluidic Templating of Polyglycerol-Based Microgels for the Encapsulation of Cells: A Comparative Study			"Kapourani, E.; Neumann, F.; Achazi, K.; Dernedde, J.; Haag, R."		Macromol Biosci			2018	10		"*Lab-On-A-Chip Devices; Animals; cell encapsulation therapies; Cell Survival; Cells, Immobilized/cytology/*metabolism; dendritic polyglycerol; droplet-based microfluidics; Glycerol/*chemistry; Hydrogels/*chemistry; Mice; microgels; NIH 3T3 Cells; Polyethylene Glycols/*chemistry; Polymers/*chemistry"				https://doi.org/10.1002/mabi.201800116		journalArticle		1616-5195 (Electronic) 1616-5187 (Linking)				Cell microencapsulation holds great promise as a therapeutic strategy for the controlled and sustained delivery of biologically relevant agents. The authors developed cell-laden microgel scaffolds with excellent long-term viabilities by combining bioorthogonal strain promoted azide-alkyne cycloaddition (SPAAC) and droplet-based microfluidic templating. Star-shaped polyglycerol hexaazide, alpha,omega-bis azido-linear polyglycerol or polyethylene glycol as well as dendritic polyglycerol-(polycyclooctyne) served as bioinert hydrogel precursors. The authors demonstrate for the first time the generation of entirely polyglycerol-based microcapsules with excellent stability and full retention of viability of the packed cells for longer than 3 weeks. As a result, our microgel particles could be used for long-term immunoisolation of cells enabling their study during encapsulation.				
KA952	Fluorescent Polymer-Single-Walled Carbon Nanotube Complexes with Charged and Noncharged Dendronized Perylene Bisimides for Bioimaging Studies			"Huth, K.; Glaeske, M.; Achazi, K.; Gordeev, G.; Kumar, S.; Arenal, R.; Sharma, S. K.; Adeli, M.; Setaro, A.; Reich, S.; Haag, R."		Small			2018	7		"*Electricity; bioimaging; Cell Death/drug effects; cytocompatibility; Dendrimers/*chemistry; Diagnostic Imaging/*methods; Fluorescence; HeLa Cells; Humans; Nanotubes, Carbon/*chemistry/toxicity; Optical Imaging; optical window; perylene bisimide; single-walled carbon nanotubes (SWNTs)"				https://doi.org/10.1002/smll.201800796		journalArticle		1613-6829 (Electronic) 1613-6810 (Linking)				Fluorescent nanomaterials are expected to revolutionize medical diagnostic, imaging, and therapeutic tools due to their superior optical and structural properties. Their inefficient water solubility, cell permeability, biodistribution, and high toxicity, however, limit the full potential of their application. To overcome these obstacles, a water-soluble, fluorescent, cytocompatible polymer-single-walled carbon nanotube (SWNT) complex is introduced for bioimaging applications. The supramolecular complex consists of an alkylated polymer conjugated with neutral hydroxylated or charged sulfated dendronized perylene bisimides (PBIs) and SWNTs as a general immobilization platform. The polymer backbone solubilizes the SWNTs, decorates them with fluorescent PBIs, and strongly improves their cytocompatibility by wrapping around the SWNT scaffold. In photophysical measurements and biological in vitro studies, sulfated complexes exhibit superior optical properties, cellular uptake, and intracellular staining over their hydroxylated analogs. A toxicity assay confirms the highly improved cytocompatibility of the polymer-wrapped SWNTs toward surfactant-solubilized SWNTs. In microscopy studies the complexes allow for the direct imaging of the SWNTs' cellular uptake via the PBI and SWNT emission using the 1st and 2nd optical window for bioimaging. These findings render the polymer-SWNT complexes with nanometer size, dual fluorescence, multiple charges, and high cytocompatibility as valuable systems for a broad range of fluorescence bioimaging studies.				
KA953	Injectable degradable PVA microgels prepared by microfluidic technology for controlled osteogenic differentiation of mesenchymal stem cells			"Hou, Y.; Xie, W.; Achazi, K.; Cuellar-Camacho, J. L.; Melzig, M. F.; Chen, W.; Haag, R."		Acta Biomater			2018	9	1	"*Microfluidics; Absorbable Implants; Biocompatible Materials/chemistry; Bone and Bones/physiology; Bone Marrow Cells/cytology; Bone Morphogenetic Protein 2/chemistry; Bone Regeneration; Bone tissue engineering; Calcium/chemistry; Cell Differentiation/*drug effects; Cell Proliferation; Cell Survival; Degradable PVA microgels; Elastic Modulus; Gels; Humans; Mesenchymal stem cells; Mesenchymal Stem Cells/*cytology; Microfluidics; Osteogenesis/*drug effects; Osteogenic differentiation; Oxygen/chemistry; Polyvinyl Alcohol/*chemistry; Regenerative Medicine; Stem Cell Transplantation; Sulfhydryl Compounds; Tissue Engineering/*methods; Tissue Scaffolds"				https://doi.org/10.1016/j.actbio.2018.07.003		journalArticle		1878-7568 (Electronic) 1742-7061 (Linking)				The direct injection of bone marrow mesenchymal stem cells (hMSCs) is a promising strategy for bone tissue engineering applications. Herein, we have developed injectable degradable poly(vinyl alcohol) (PVA) microgels loaded with hMSCs and growth factors and prepared by a high-throughput microfluidic technology. The PVA-based microgels with tunable mechanical and degradable properties were composed of vinyl ether acrylate-functionalized PVA (PVA-VEA) and thiolated PVA-VEA (PVA-VEA-SH) through a Michael-type crosslinking reaction under mild conditions. The hMSCs sustain high viability in PVA microgels, and cell proliferation and migration behaviors can easily be adjusted by varying crosslinking densities of PVA microgels. Additionally, bone morphogenetic protein-2 (BMP-2) co-encapsulated into the microgel environments enhanced osteogenic differentiation of hMSCs as indicated by a significant increase in alkaline phosphatase activity, calcium content, and Runx2 and OPN gene expression levels. These results demonstrate the degradable PVA microgels with tailored stem cell microenvironments and controlled release profile of the growth factor to promote and direct differentiation. These PVA-based microgels have promising potential as ideal cell vehicles for applications in regenerative medicine. STATEMENT OF SIGNIFICANCE: Stem cell transplantation by an injectable, minimally invasive method has great and promising potential for various injuries, diseases, and tissue regeneration. However, its applications are largely limited owing to the low cell retention and engraftment at the lesion location after administration. We have developed an injectable degradable poly(vinyl alcohol) (PVA) microgel prepared by a high-throughput microfluidic technology and co-loaded with bone marrow mesenchymal stem cells (hMSCs) and growth factor to protect the stem cells from harsh environmental stress and realize controlled cell differentiation in well-defined microenvironments for bone regeneration. We demonstrated that these degradable PVA microgels can be used as stem cell scaffolds with tailored cell microenvironments and controlled release profile of growth factor to promote and direct differentiation. We are convinced that these PVA-based microgels have promising potential in the future as cellular scaffolds for applications in regenerative medicine.				
KA954	Heterobifunctional Dyes: Highly Fluorescent Linkers Based on Cyanine Dyes			"Wycisk, V.; Achazi, K.; Hirsch, O.; Kuehne, C.; Dernedde, J.; Haag, R.; Licha, K."		ChemistryOpen			2017	6		"antibodies; conjugation; dyes/pigments; fluorescence; heterobifunctional linkers"				https://doi.org/10.1002/open.201700013		journalArticle		2191-1363 (Print) 2191-1363 (Electronic) 2191-1363 (Linking)				Herein, we present a new synthetic route to cyanine-based heterobifunctional dyes and their application as fluorescent linkers between polymers and biomolecules. The synthesized compounds, designed in the visible spectral range, are equipped with two different reactive groups for highly selective conjugation under physiological conditions. By applying indolenine precursors with functionalized benzenes, we achieved water-soluble asymmetric cyanine dyes bearing maleimido and N-hydroxysuccinimidyl functionalities in a three-step synthesis. Spectroscopic characterization revealed good molar absorption coefficients and moderate fluorescence quantum yields. Further reaction with polyethylene glycol yielded dye-polymer conjugates that were subsequently coupled to the antibody cetuximab, often applied in cancer therapy. Successful coupling was confirmed by mass shifts detected by gel electrophoresis. Receptor-binding studies and live-cell imaging revealed that labeling did not alter the biological function. In sum, we provided a successful synthetic pathway to rigid heterobifunctional cyanine dyes that are applicable as fluorescent linkers, for example, for connecting antibodies with macromolecules. Our approach contributes to the field of bioconjugation chemistry, such as antibody-drug conjugates by combining diagnostic and therapeutic approaches.				
KA955	Active Antibacterial and Antifouling Surface Coating via a Facile One-Step Enzymatic Cross-Linking			"Wu, C.; Schwibbert, K.; Achazi, K.; Landsberger, P.; Gorbushina, A.; Haag, R."		Biomacromolecules			2017	1	9	"Anti-Bacterial Agents/chemistry/*pharmacology; Bacterial Adhesion; Coated Materials, Biocompatible/chemistry; Glass/*chemistry; Glucose Oxidase/*metabolism; Glucose/metabolism; Glycerol/*chemistry; Horseradish Peroxidase/*metabolism; Hydrogel, Polyethylene Glycol Dimethacrylate/*chemistry; Hydrogen Peroxide/metabolism; Oxidation-Reduction; Polymers/*chemistry; Pseudomonas putida/drug effects; Staphylococcus aureus/drug effects"				https://doi.org/10.1021/acs.biomac.6b01527		journalArticle		1526-4602 (Electronic) 1525-7797 (Linking)				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 H(2)O(2) 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 (OD(540) = 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 H(2)O(2) 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.				
KA956	Combination of Surface Charge and Size Controls the Cellular Uptake of Functionalized Graphene Sheets			"Tu, Z.; Achazi, K.; Schulz, A.; M lhaupt, R.; Thierbach, S.; R hl, E.; Adeli, M.; Haag, R."		Advanced Functional Materials			2017	9	6	"cancer-cells; cellular uptake; drug-delivery; endocytic pathways; endocytosis; gold nanoparticles; graphene; in-vivo biodistribution; nano-graphene; oxide nanosheets; platform; polyglycerol; quantum dots; sheet size; surface charge"				https://doi.org/10.1002/adfm.201701837		journalArticle		1616-301x				A fundamental issue for biomedical applications of graphene is the correlation between its physicochemical properties and cellular uptake mechanism. However, such studies are challenging due to the intrinsic polydispersity of graphene. In this work, a series of water soluble graphene sheets with the same polymer coverage, density of functional groups, and fluorescence intensity but three different sizes and surface charges are produced. The effect of the latter two factors and their combination on the mechanism of cellular uptake and intracellular pathways of these defined nanosheets is investigated via confocal and Raman microscopies. While positively (-NH3+) and negatively (-OSO3-) charged sheets show an energy dependent uptake, their neutral analogs do not show any significant uptake. The cellular uptake efficacy of positively charged graphene sheets is independent of the size and occurs both through phagocytosis and clathrin-mediated endocytosis pathways. However, cellular uptake efficacy of graphene sheets with negative surface charge strongly depends on the size of the sheets. They cross the membrane mainly through phagocytosis and sulfate-receptor-mediated endocytosis. This study demonstrates that the impact of the size of graphene derivatives on their cellular uptake pathways highly depends on their surface charges and vice versa.				
KA957	Aggregation Behavior of Non-ionic Twinned Amphiphiles and Their Application as Biomedical Nanocarriers			"Singh, A. K.; Thota, B. N. S.; Schade, B.; Achazi, K.; Khan, A.; Bottcher, C.; Sharma, S. K.; Haag, R."		Chemistry, an Asian journal			2017	7	18	"cryo-TEM; nanocarriers; Nile Red; nimodipine; self-assembly; twinned amphiphiles"				https://doi.org/10.1002/asia.201700450		journalArticle		1861-471X (Electronic) 1861-471X (Linking)				A new class of twinned amphiphiles was developed by conjugating a pair of hydrophilic head groups from mPEG chains (M(n) : 350 or 1000) and a pair of hydrophobic segments from linear alkyl chains (C(11) or C(18) ) through a novel spacer synthesized from glycerol and p-hydroxybenzoic acid. The aggregation phenomena of the amphiphiles were proven by DLS and fluorescence experiments, whereas size and morphology of the aggregates were evaluated by cryo-TEM. The measurements proved the formation of globular, thread-like or rod-like micelles as well as planar double-layer assemblies, depending on the amphiphile's molecular structure. The applicability of these non-ionic amphiphilic systems as nanocarriers for hydrophobic guest molecules was demonstrated by encapsulating a hydrophobic dye, Nile Red, and a hydrophobic drug, Nimodipine. The transport capacity results for both Nimodipine and Nile Red prove them as a promising candidate for drug delivery.				
KA958	Fabrication of nanostructures through self-assembly of non-ionic amphiphiles for biomedical applications			"Prasad, S.; Achazi, K.; B ttcher, C.; Haag, R.; Sharma, S. K."		Rsc Advances			2017			"block-copolymers; curcumin encapsulation; cyclopolymerization; dendritic amphiphiles; dendronized polymers; drug-delivery; gemini surfactants; nanocarriers; nanoparticles; transport behavior"				https://doi.org/10.1039/c6ra28654b		journalArticle		2046-2069				Fabrication of self-assembled nanostructures with defined size and morphology represents a formidable challenge and thus, has gained tremendous momentum in research because of their potential applications in various biological systems. Herein, we report on the synthesis of novel non-ionic amphiphiles using 2,2-di(prop-2-yn-1-yl) propane-1,3-diol as a core further functionalized with poly(ethylene glycol) monomethyl ether and alkyl chains employing a chemo-enzymatic approach. Surface tension and fluorescence measurements along with dynamic light scattering studies revealed that all of the amphiphilic systems spontaneously self-assemble in aqueous solution, which is further supplemented by cryogenic transmission electron microscopy. The solubilization behavior of these systems as evidenced from UV-Vis and fluorescence spectroscopy and high performance liquid chromatography suggested the effective encapsulation of hydrophobic entities like Nile red, nimodipine, curcumin and dexamethasone. A comparative study with a standard excipient, Cremophor (R) ELP demonstrated that our nanocarriers exhibited superior/equivalent solubilization behavior for curcumin. Confocal laser scanning microscopy revealed efficient uptake of encapsulated dye in the cytosol of lung cancer cells, thus suggesting, that the reported amphiphilic systems can transport drugs into cells. A study of cytotoxicity showed that the synthesized amphiphilic systems are non-cytotoxic at the concentrations studied. The release profile of encapsulated Nile red incubated with/without a hydrolase enzyme Candida antarctica lipase demonstrated that the dye is stable in the amphiphilic nanostructures in the absence of enzyme for up to 12 days, however, more than 90% release of the dye occurred in 12 days when incubated with lipase. The results advocate the potential of these nanostructures as prospective drug delivery vehicles.				
KA959	Lipase-mediated synthesis of sugar-PEG-based amphiphiles for encapsulation and stabilization of indocyanine green			"Khatri, V.; Bhatia, S.; Achazi, K.; Deep, S.; Kohli, E.; Sharma, S. K.; Haag, R.; Prasad, A. K."		Rsc Advances			2017			"cancer-cells; chemotherapy; copolymers; drug-delivery; micelles; nanocapsules; nanoparticles; nanospheres; photothermal therapy; polymers"				https://doi.org/10.1039/c7ra04994c		journalArticle		2046-2069				Indocyanine green (ICG) is a near-infrared dye for wide-ranging applications, but its utility for biological studies is limited due to poor aqueous stability and concentration-dependent aggregation. Aqueous polymeric micelles/micellar aggregates of amphiphilic copolymers could be used to protect indocyanine green (ICG) by encapsulation, which is used in laser-mediated photothermal therapy (PTT) and photodynamic therapy (PDT). The sugar-PEG-based amphiphilic copolymers were synthesized using Novozym 435-catalyzed transesterification reaction under bulk conditions for encapsulation of ICG. A dye loading study revealed that micelles derived from copolymers having decanoylated and myristoylated sugar moieties encapsulate 62% and 92% of the ICG, respectively, with a multi-fold increase in its aqueous stability. Furthermore, an efficient internalization of micelles of acylated amphiphilic copolymers in aqueous medium was demonstrated by incubating cells with Nile red-encapsulated amphiphiles.