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
KA930	Biodegradable Dendritic Polyglycerol Sulfate for the Delivery and Tumor Accumulation of Cytostatic Anticancer Drugs			"Cherri, M.; Ferraro, M.; Mohammadifar, E.; Quaas, E.; Achazi, K.; Ludwig, K.; Grotzinger, C.; Schirner, M.; Haag, R."		ACS Biomater Sci Eng			2021	6	14	"*Antineoplastic Agents; *Cytostatic Agents; *Neoplasms/drug therapy; cancer therapy; drug delivery systems; drug encapsulation; Glycerol; Humans; Polymers; Sulfates; sunitinib; tumor accumulation"				https://doi.org/10.1021/acsbiomaterials.1c00439		journalArticle		2373-9878 (Electronic) 2373-9878 (Linking)				Targeted delivery and extended blood circulation of anticancer drugs have been the challenges for decreasing the adverse side effects and improving the therapeutic efficiency in cancer chemotherapy. Herein, we present a drug delivery system (DDS) based on biodegradable dendritic polyglycerol sulfate-bearing poly(caprolactone) (dPGS-PCL) chains, which has been synthesized on 20 g scale using a straightforward two-step protocol. In vivo fluorescence imaging demonstrated a significant accumulation of the DDS in the tumor environment. Sunitinib, an anticancer drug, was loaded into the DDS and the drug-induced toxicity was investigated in vitro and in vivo. The drug encapsulated in dPGS-PCL and the free drug showed similar toxicities in A431 and HT-29 cells, and the cellular uptake was comparable. The straightforward and large-scale synthesis, the organic solvent-free drug-loading approach, together with the tumor targetability of the biodegradable dendritic polyglycerols, render this copolymer a promising candidate for targeted cancer nanomedicine drug delivery systems.				
KA931	Amphiphilic Co-polypeptides Self-Assembled into Spherical Nanoparticles for Dermal Drug Delivery			"Ahmadi, V.; Zabihi, F.; Rancan, F.; Staszak, A. A.; Nie, C. X.; Dimde, M.; Achazi, K.; Wiehe, A.; Vogt, A.; Haag, R."		Acs Applied Nano Materials			2021	7	23	"acid n-carboxyanhydrides; alpha-amino-acids; amphiphilic block-co-polypeptide; block-copolymer micelles; cellular uptake; dermal drug delivery; gamma-acetyldiaminobutyrate; nanocarrier; one-pot; ph-sensitive; phosgene-free synthesis; ring-opening polymerization; self-assembly; skin penetration; surface-charge"				https://doi.org/10.1021/acsanm.1c00693		journalArticle		2574-0970				Poly(L-glutamic acid)-b-poly(N.-acetyl-L-2,4-diaminobutyric acid), P(Glu-b-NADA), amphiphilic block-co-polypeptides with different hydrophobic/hydrophilic ratios were synthesized as drug carriers for dermal delivery. The block-copolypeptides were prepared using ring-opening polymerization (ROP) of gamma-benzyl L-glutamate N-carboxyanhydride and polycondensation of the activated urethane derivative of N-gamma-acetyl-L-2,4-diaminobutyric acid. Structures and conjugations of two blocks were successfully confirmed by H-1 NMR, FTIR, DOSY NMR, GPC, and TGA. The nanocarriers were loaded with 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (m-THPP), a close congener of the approved photosensitizer 5,10,15,20-tetrakis(3hydroxyphenyl)chlorin (m-THPC, temoporfin), and the loading capacity was found to be dependent on the composition of the block-co-polypeptides. Among the synthesized polymers, P(Glu(55)-b-NADA(20)) with moderate hydrophobic content showed the highest drug loading capacity of 4 wt % and self-aggregated into spherical nanoparticles with a size of 180-200 nm, which was confirmed by TEM and DLS. In an in vitro drug release study, P(Glu(55)-b-NADA(20)) could release m-THPP in a controllable manner. Furthermore, the synthesized polymer P(Glu(55)-b-NADA(20)) did not show high toxicity against HaCaT and HeLa cells up to 1000 and 500 mu g mL(-1), respectively, in an in vitro cell viability assay. Finally, it was shown in an ex vivo skin penetration study that the ionic amphiphilic block co-polypeptide enhanced the m-THPP penetration into human skin compared to base cream up to a factor of 12. m-THPP was released from P(Glu(55)-b-NADA(20)) to the viable epidermis while the polymer was deposited in the skin's stratum corneum. Taking advantage of its excellent biodegradability, the low cytotoxcity, and efficient skin penetration, the synthesized block-co-polypeptide has the potential for future topical delivery systems.				
KA932	One-pot gram-scale synthesis of virucidal heparin-mimicking polymers as HSV-1 inhibitors			"Ahmadi, V.; Nie, C.; Mohammadifar, E.; Achazi, K.; Wedepohl, S.; Kerkhoff, Y.; Block, S.; Osterrieder, K.; Haag, R."		Chem Commun (Camb)			2021	11	11	"*Antiviral Agents/pharmacology/chemical synthesis/chemistry; *Glycerol/chemistry/pharmacology/chemical synthesis; *Heparin/chemistry/pharmacology/chemical synthesis; *Herpesvirus 1, Human/drug effects; *Polymers/chemistry/pharmacology/chemical synthesis; Animals; Chlorocebus aethiops; Molecular Structure; Vero Cells"				https://doi.org/10.1039/d1cc04703e		journalArticle		1364-548X (Electronic) 1359-7345 (Linking)				A straightforward and gram-scale synthesis method was developed to engineer highly sulfated hyperbranched polyglycerol bearing sulfated alkyl chains. The compounds with shorter alkyl chains showed multivalent virustatic inhibition against herpes simplex virus type 1 (HSV-1), similar to heparin. In contrast, the compound with the longest alkyl chains irreversibly inhibited the virus.				
KA933	Understanding the Interaction of Polyelectrolyte Architectures with Proteins and Biosystems			"Achazi, K.; Haag, R.; Ballauff, M.; Dernedde, J.; Kizhakkedathu, J. N.; Maysinger, D.; Multhaup, G."		Angew Chem Int Ed Engl			2021	2	19	"Antineoplastic Agents/chemistry/pharmacology; Cell Survival/drug effects; complementary binding; counterion release; DNA/*chemistry/metabolism; Drug Carriers/chemistry; Glycosaminoglycans/chemistry/metabolism; heparin; Humans; inflammation; polyelectrolytes; Polyelectrolytes/*chemistry/metabolism; Protein Binding; Proteins/*chemistry/metabolism; Thermodynamics"				https://doi.org/10.1002/anie.202006457		journalArticle		1521-3773 (Electronic) 1433-7851 (Print) 1433-7851 (Linking)				The counterions neutralizing the charges on polyelectrolytes such as DNA or heparin may dissociate in water and greatly influence the interaction of such polyelectrolytes with biomolecules, particularly proteins. In this Review we give an overview of studies on the interaction of proteins with polyelectrolytes and how this knowledge can be used for medical applications. Counterion release was identified as the main driving force for the binding of proteins to polyelectrolytes: Patches of positive charge become multivalent counterions of the polyelectrolyte and lead to the release of counterions from the polyelectrolyte and a concomitant increase in entropy. This is shown from investigations on the interaction of proteins with natural and synthetic polyelectrolytes. Special emphasis is paid to sulfated dendritic polyglycerols (dPGS). The Review demonstrates that we are moving to a better understanding of charge-charge interactions in systems of biological relevance. Research along these lines will aid and promote the design of synthetic polyelectrolytes for medical applications.				
KA934	Non-ionic PEG-oligoglycerol dendron conjugated nano-carriers for dermal drug delivery			"Rashmi; Zabihi, F.; Singh, A. K.; Achazi, K.; Schade, B.; Hedtrich, S.; Haag, R.; Sharma, S. K."		Int J Pharm			2020	4	30	"A549 Cells; Amphiphiles; Anthracenes/administration & dosage/*chemistry/metabolism; Cell Survival/drug effects/physiology; Dermal delivery; Drug Carriers/administration & dosage/*chemistry/metabolism; Drug Delivery Systems/*methods; HeLa Cells; Humans; MCF-7 Cells; Nanocarrier; Nanoparticles/administration & dosage/*chemistry/metabolism; Oligoglycerol; Organ Culture Techniques; Polyethylene Glycols/administration & dosage/*chemistry/metabolism; Skin Absorption/drug effects/*physiology"				https://doi.org/10.1016/j.ijpharm.2020.119212		journalArticle		1873-3476 (Electronic) 0378-5173 (Linking)				A new class of non-ionic amphiphiles have been synthesised using a combination of polyethylene glycol (PEG) and oligoglycerol dendrons as hydrophilic units and an alkoxy aryl moiety as hydrophobic unit. The resulting amphiphiles were found to aggregate in aqueous medium. Their aggregation behaviour was studied using dynamic light scattering (DLS), fluorescence spectroscopy, and cryogenic electron microscopy (cryo-TEM). The inner hydrophobic core of these aggregates in aqueous medium is capable of encapsulating lipophilic guest molecules. The encapsulation behaviour was studied using Nile red as a hydrophobic dye as well as Curcumin and Dexamethasone as hydrophobic drug candidates. Furthermore, for biological evaluation, cytotoxicity and cellular uptake was studied using different cancer cell lines. The biomedical application of synthesised amphiphiles was further investigated for dermal drug delivery on excised human skin using Nile red encapsulated in the nanocarrier. The release profile of drug/dye encapsulated amphiphiles was studied under physiochemical conditions in the presence of immobilized lipase Novozym 435.				
KA935	Stimuli-responsive non-ionic Gemini amphiphiles for drug delivery applications			"Rashmi; Singh, A. K.; Achazi, K.; Ehrmann, S.; B ttcher, C.; Haag, R.; Sharma, S. K."		Polymer Chemistry			2020	11	14	"aggregation behavior; block-copolymer; carriers; glutathione; micelles; nanocarriers; polyglycerol; surfactants"				https://doi.org/10.1039/d0py01040e		journalArticle		1759-9954				A series of six novel disulfide-bond-linked Gemini amphiphiles have been synthesized using polyethylene glycol (PEG) as hydrophilic units and alkoxy aryl moieties as hydrophobic units. The self-assembling behaviour of the resulting amphiphiles was studied using fluorescence spectroscopy and dynamic light scattering (DLS). The inner hydrophobic core with an alkyl and fluoroalkyl chain aggregates differently in aqueous medium as evidenced by a cryo-TEM study. Also they are found to be capable of encapsulating a lipophilic guest. The encapsulation behaviour was studied using Nile red as a model hydrophobic dye and extended further by including curcumin and an anti-cancerous drug doxorubicin. Furthermore, for biological evaluation, their cytotoxicity and cellular uptake were studied. The presence of stimuli responsive disulfide linkages and the ester functionality provides the possibility of redox responsive and enzymatic release of the encapsulated cargo, which was studied by using various concentrations of glutathione (GSH) and an immobilized lipase Novozym 435.				
KA936	Oligo-glycerol based non-ionic amphiphilic nanocarriers for lipase mediated controlled drug release			"Parmanand; Mittal, A.; Singh, A. K.; Aarti; Achazi, K.; Nie, C.; Haag, R.; Sharma, S. K."		Rsc Advances			2020	10	7	"building-blocks; cancer; delivery; dendrimer; nanoparticles; polymer therapeutics"				https://doi.org/10.1039/d0ra07392j		journalArticle		2046-2069 (Electronic) 2046-2069 (Linking)				A new class of non-ionic amphiphiles is synthesized using a diaryl derivative of diglycerol as a central core and functionalizing it with long alkyl chains (C-12/C-15) and monomethoxy PEG moiety (M (n): 350/550) by following a chemo-enzymatic approach. The aggregation behavior of the amphiphiles in aqueous medium is studied by using dynamic light scattering (DLS) and fluorescence spectroscopy, whereas the size and morphology of the aggregates are studied by transmission electron microscopy (TEM). A hydrophobic dye, Nile red and a hydrophobic drug, nimodipine, are used to demonstrate the nano-carrier capability of these non-ionic amphiphilic systems and the results are compared with amphiphilic analogues obtained from the triaryl derivatives of triglycerol. The in vitro controlled release of the encapsulated dye is successfully carried out in the presence of immobilized Candida antarctica lipase (Novozym 435). Furthermore, cytotoxicity data is also collected which suggests that the amphiphiles are suitable for biomedical applications.				
KA937	Fabrication of oligo-glycerol based hydrolase responsive amphiphilic nanocarriers			"Mittal, A.; Singh, A. K.; Kumar, A.; Parmanand; Achazi, K.; Haag, R.; Sharma, S. K."		Polymers for Advanced Technologies			2020	6		"amphiphile; block-copolymer; chemistry; cytotoxicity; dendrimer; drug-delivery; encapsulation; micelles; nanoparticles; nanostructures; polymers; self-assembly"				https://doi.org/10.1002/pat.4851		journalArticle		1042-7147				Herein, we report on the synthesis of a new class of novel non-ionic amphiphiles using triglycerol as a core, which is further functionalized with hydrophilic units poly(ethylene glycol) monomethyl ether (M-n: 350 and 550) and a pair of hydrophobic alkyl chains (C-18 or C-15) via chemo-enzymatic approach. Fluorescence measurements and dynamic light scattering studies showed that all of the synthesized amphiphilic systems spontaneously self- assemble in aqueous solution, which is further confirmed by the transmission electron microscopy. Encapsulation of hydrophobic moieties like Nile red and nimodipine was studied using ultraviolet-visible (UV-vis) and fluorescence spectrometer techniques. A cytotoxicity study of the amphiphiles using A549, HeLa, and MCF7 cell, which showed that all of the synthesized nanocarriers are well tolerated at the concentrations studied. The release profile of encapsulated Nile red in synthesized amphiphilic system was studied in the presence of the immobilized enzyme (Novozym 435).				
KA938	Chemoenzymatic Synthesis of D-Glucitol-Based Non-Ionic Amphiphilic Architectures as Nanocarriers			"Manchanda, P.; Achazi, K.; Verma, D.; Bottcher, C.; Haag, R.; Sharma, S. K."		Polymers (Basel)			2020	6	25	"Candida antarctica lipase; click chemistry; cyto-compatible; D-Glucitol; nanocarrier; non-ionic amphiphiles"				https://doi.org/10.3390/polym12061421		journalArticle		2073-4360 (Electronic) 2073-4360 (Linking)				Newer non-ionic amphiphiles have been synthesized using biocompatible materials and by following a greener approach i.e., D-glucitol has been used as a template, and hydrophobic and hydrophilic segments were incorporated on it by using click chemistry. The hydrophilic segments in turn were prepared from glycerol using an immobilized Candida antarctica lipase (Novozym-435)-mediated chemoenzymatic approach. Surface tension measurements and dynamic light scattering studies reflect the self-assembling behavior of the synthesized amphiphilic architectures in the aqueous medium. The results from UV-Vis and fluorescence spectroscopy establish the encapsulation of guests in the hydrophobic core of self-assembled amphiphilic architectures. The results of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay indicate that the amphiphiles are well tolerated by the used A549 cell lines at all tested concentrations.				
KA939	Cells Undergo Major Changes in the Quantity of Cytoplasmic Organelles after Uptake of Gold Nanoparticles with Biologically Relevant Surface Coatings			"Kepsutlu, B.; Wycisk, V.; Achazi, K.; Kapishnikov, S.; Perez-Berna, A. J.; Guttmann, P.; Cossmer, A.; Pereiro, E.; Ewers, H.; Ballauff, M.; Schneider, G.; McNally, J. G."		ACS Nano			2020	2	25	"3D ultrastructural analysis; cellular trafficking; confocal laser scanning microscopy; cryo-soft X-ray tomography; Cytoplasm/chemistry/*metabolism; cytoplasmic remodeling; dendritic polyglycerol sulfate; Glycerol/chemistry/*metabolism; Gold/chemistry/*metabolism; Humans; Metal Nanoparticles/*chemistry; Organelles/chemistry/*metabolism; Particle Size; polyethylenimine; Polymers/chemistry/*metabolism; Sulfates/chemistry/*metabolism; Surface Properties; Tomography, X-Ray; Tumor Cells, Cultured"				https://doi.org/10.1021/acsnano.9b09264		journalArticle		1936-086X (Electronic) 1936-0851 (Linking)				"Here, we use cryo soft X-ray tomography (cryo-SXT), which delivers 3D ultrastructural volumes of intact cells without chemical fixation or staining, to gain insight about nanoparticle uptake for nanomedicine. We initially used dendritic polyglycerol sulfate (dPGS) with potential diagnostic and therapeutic applications in inflammation. Although dPGS-coated gold nanoparticle (dPGS-AuNP) uptake followed a conventional endocytic/degradative pathway in human lung epithelial cell lines (A549), with cryo-SXT, we detected approximately 5% of dPGS-AuNPs in the cytoplasm, a level undetectable by confocal light microscopy. We also observed approximately 5% of dPGS-AuNPs in a rarely identified subcellular site, namely, lipid droplets, which are important for cellular energy metabolism. Finally, we also found substantial changes in the quantity of cytoplasmic organelles upon dPGS-AuNP uptake over the 1-6 h incubation period; the number of small vesicles and mitochondria significantly increased, and the number of multivesicular bodies and the number and volume of lipid droplets significantly decreased. Although nearly all organelle numbers at 6 h were still significantly different from controls, most appeared to be returning to normal levels. To test for generality, we also examined cells after uptake of gold nanoparticles coated with a different agent, polyethylenimine (PEI), used for nucleic acid delivery. PEI nanoparticles did not enter lipid droplets, but they induced similar, albeit less pronounced, changes in the quantity of cytoplasmic organelles. We confirmed these changes in organelle quantities for both nanoparticle coatings by confocal fluorescence microscopy. We suggest this cytoplasmic remodeling could reflect a more common cellular response to coated gold nanoparticle uptake."