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Biogenic Nanotherapeutics

Jun Prof Dr Gregor Fuhrmann

The combination of incorrect and overly frequent application of antibiotics and insufficient hygiene measures in hospitals leads to a worldwide rise in the number of resistant germs for which ever less effective therapies exist. The scientists of the "Biogenic Nanotherapeutics" group develop intelligent mechanisms of action and nano-systems that transport known antibiotics specifically to infected sites in the human body. In their work, they use modern biomimetic systems that utilise mechanisms found in nature or are derived from them. This allows for an effective control of pathogenic bacteria with minimal adverse effects.

Our research and approach

Our main focus is on the characterisation of extracellular vesicles (EVs) as natural information transporters. EVs are nano-particles of 50-200 nm in size that are produced naturally by virtually all eukaryotic and prokaryotic cells and are either evaginated from the cell surface or produced in and released from multi-vesicular compartments. EVs consists of a lipid double layer, bear signal molecules, such as proteins or nucleic acids (e.g. microRNA), and are very efficient cell-cell communicators that migrate from one cell type to another, interact with the target cell by means of their surface and membrane proteins and thus transfer signal molecules in a highly specific manner.

We developed methods that allow us to load EVs with different model drugs and we can study their interaction with cells using real-time microscopy. Afterwards, we aim at incorporating these drug-loaded EVs in a pharmaceutical formulation and evaluate its efficiency in complex in vitro and in vivo models.

Interestingly, not only mammalian cells make use of EVs, but bacteria also utilize so-called outer membrane vesicles (OMVs) for their mutual interaction by transporting these communication molecules specifically within a bacterial colony or a biofilm. Moreover, OMVs of certain bacteria, such as e.g. Myxobacteria, contain hydrolytic factors for the fight against other bacteria which compete for biological niches. We isolate and characterise OMVs of different bacteria and study how these interact with other bacteria or human cells and which physiological role they have. New therapeutic approaches to combat bacterial infections can be derived from these studies.

In addition to the development of biogenic agent carriers we are also interested in real-time analysis methods imaging the stability and activity of agents in complex in vitro and in vivo models by means of a non-invasive technique. We have successfully developed a fluorescence-based system for the analysis of therapeutic enzymes and we noted significant differences to the tests in a test tube. We aim to extend the fluorescence-based measuring principle to other diseases, such as inflammations and infections.

Team members

Publications

2020

Probiomimetics-Novel Lactobacillus-Mimicking Microparticles Show Anti-Inflammatory and Barrier-Protecting Effects in Gastrointestinal Models

Kuhn T, Koch M, Fuhrmann G (2020)

Small (Weinheim an der Bergstrasse, Germany)DOI: 10.1002/smll.202003158

Diffusion and transport of extracellular vesicles

Fuhrmann G (2020)

Nature Nanotechnology, 15 (3): 168-169DOI: 10.1038/s41565-020-0651-3

Coupling quaternary ammonium surfactants to the surface of liposomes improves both antibacterial efficacy and host cell biocompatibility

Montefusco-Pereira C, Formicola B, Goes A, Re F, Marrano C, Mantegazza F, Carvalho-Wodarz C, Fuhrmann G, Caneva E, Nicotra F, Lehr C, Russo L (2020)

European Journal of Pharmaceutics and Biopharmaceutics, 149: 12-20DOI: 10.1016/j.ejpb.2020.01.013

Liver-derived extracellular vesicles: A cell by cell overview to isolation and characterization practices

Zivko C, Fuhrmann G, Luciani P (2020)

Biochimica et Biophysica Acta - General SubjectsDOI: 10.1016/j.bbagen.2020.129559

Streptococcal Extracellular Membrane Vesicles Are Rapidly Internalized by Immune Cells and Alter Their Cytokine Release

Mehanny M, Koch M, Lehr C, Fuhrmann G (2020)

Frontiers in immunology, 11DOI: 10.3389/fimmu.2020.00080

2019

Engineering strategies for oral therapeutic enzymes to enhance their stability and activity

Lapuhs P, Fuhrmann G (2019)

Book, 1148DOI: 10.1007/978-981-13-7709-9_8

Author Correction: Extracellular vesicles protect glucuronidase model enzymes during freeze-drying (Scientific Reports, (2018), 8, 1, (12377), 10.1038/s41598-018-30786-y)

Frank J, Richter M, Rossi C, Lehr C, Fuhrmann K, Fuhrmann G (2019)

Scientific Reports, 9 (1)DOI: 10.1038/s41598-019-48221-1

Corrigendum to biocompatible bacteria-derived vesicles show inherent antimicrobial activity (Journal of Controlled Release (2018) 290 (46–55), (S0168365918305698) (10.1016/j.jconrel.2018.09.030))

Schulz E, Goes A, Garcia R, Panter F, Koch M, Müller R, Fuhrmann K, Fuhrmann G (2019)

Journal of Controlled Release, 293: 155-157DOI: 10.1016/j.jconrel.2018.11.027

Toll-Like Receptor 2 Release by Macrophages: An Anti-inflammatory Program Induced by Glucocorticoids and Lipopolysaccharide

Hoppstädter J, Dembek A, Linnenberger R, Dahlem C, Barghash A, Fecher-Trost C, Fuhrmann G, Koch M, Kraegeloh A, Huwer H, Kiemer A (2019)

Front. Immunol., 10DOI: 10.3389/fimmu.2019.01634

Hot EVs – how temperature affects extracellular vesicles

Schulz E, Karagianni A, Koch M, Fuhrmann G (2019)

European Journal of Pharmaceutics and BiopharmaceuticsDOI: 10.1016/j.ejpb.2019.11.010

Extracellular Vesicles—Connecting Kingdoms

Woith E, Fuhrmann G, Melzig M (2019)

International journal of molecular sciences, 20 (22)DOI: 10.3390/ijms20225695

Evaluation of the Storage Stability of Extracellular Vesicles

Richter M, Fuhrmann K, Fuhrmann G (2019)

Journal of visualized experiments : JoVE (147)DOI: 10.3791/59584

2018

Luminal coating of the intestine

Fuhrmann G (2018)

Nature Materials, 17 (9): 754-755DOI: 10.1038/s41563-018-0143-0

Extracellular vesicles protect glucuronidase model enzymes during freeze-drying

Frank J, Richter M, Rossi C, Lehr C, Fuhrmann K, Fuhrmann G (2018)

Scientific Reports, 8 (1)DOI: 10.1038/s41598-018-30786-y

Biocompatible bacteria-derived vesicles show inherent antimicrobial activity

Schulz E, Goes A, Garcia R, Panter F, Koch M, Müller R, Fuhrmann K, Fuhrmann G (2018)

Journal of Controlled Release, 290: 46-55DOI: 10.1016/j.jconrel.2018.09.030

Biogenic and Biomimetic Carriers as Versatile Transporters To Treat Infections

Goes A, Fuhrmann G (2018)

ACS infectious diseases, 4 (6): 881-892DOI: 10.1021/acsinfecdis.8b00030

Engineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy

Fuhrmann G, Chandrawati R, Parmar P, Keane T, Maynard S, Bertazzo S, Stevens M (2018)

Advanced materials (Deerfield Beach, Fla.), 30 (15)DOI: 10.1002/adma.201706616

2017

Recent advances in oral delivery of macromolecular drugs and benefits of polymer conjugation

Kathrin Fuhrmann G (2017)

Current Opinion in Colloid & Interface Science, 31: 67-74DOI: 10.1016/j.cocis.2017.07.002

Extracellular vesicles - A promising avenue for the detection and treatment of infectious diseases?

Fuhrmann G, Neuer A, Herrmann I (2017)

Eur J Pharm Biopharm, 118: 56-61DOI: 10.1016/j.ejpb.2017.04.005

2016

Erratum: Sustained gastrointestinal activity of dendronized polymer-enzyme conjugates (Nature Chemistry (2013) 5 (582-589))

Fuhrmann G, Grotzky A, Lukic R, Matoori S, Luciani P, Yu H, Zhang B, Walde P, Schlüter A, Gauthier M, Leroux J (2016)

Nature chemistry, 8 (3)DOI: 10.1038/nchem.2458

2015

Extracellular Stiffness Modulates the Expression of Functional Proteins and Growth Factors in Endothelial Cells

Santos L, Fuhrmann G, Juenet M, Amdursky N, Horejs C, Campagnolo P, Stevens M (2015)

Advanced healthcare materials, 4 (14): 2056-2063DOI: 10.1002/adhm.201500338

Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrins

Fuhrmann G, Serio A, Mazo M, Nair R, Stevens M (2015)

Journal of Controlled Release, 205: 35-44DOI: 10.1016/j.jconrel.2014.11.029

Cell-derived vesicles for drug therapy and diagnostics

Fuhrmann G, Herrmann I, Stevens M (2015)

Nano Today, 10 (3): 397-409DOI: 10.1016/j.nantod.2015.04.004

2013

Polymer-enzyme conjugates for oral drug delivery applications

Fuhrmann G, Gauthier M, Leroux J (2013)

Chimia, 67 (9)DOI: 10.2533/chimia.2013.685

Sustained gastrointestinal activity of dendronized polymer-enzyme conjugates

Fuhrmann G, Grotzky A, Lukic R, Matoori S, Luciani P, Yu H, Zhang B, Walde P, Schlüter A, Gauthier M, Leroux J (2013)

Nature chemistry, 5 (7): 582-589DOI: 10.1038/nchem.1675

Celiac disease: A challenging disease for pharmaceutical scientists

Matoori S, Fuhrmann G, Leroux J (2013)

Pharmaceutical research, 30 (3): 619-626DOI: 10.1007/s11095-012-0951-x

2012

The copolymer P(HEMA-co-SS) binds gluten and reduces immune response in gluten-sensitized mice and human tissues

Pinier M, Fuhrmann G, Galipeau H, Rivard N, Murray J, David C, Drasarova H, Tuckova L, Leroux J, Verdu E (2012)

Gastroenterology, 142 (2): 316-325DOI: 10.1053/j.gastro.2011.10.038

Erratum: In vivo fluorescence imaging of exogenous enzyme activity in the gastrointestinal tract (Proceedings of the National Academy of Sciences of the United States of America (2011) 108, 22 (9032-9037) DOI: 10.1073/pnas. 1100285108)

Fuhrmann G, Leroux J (2012)

Proceedings of the National Academy of Sciences of the United States of America, 109 (42)DOI: 10.1073/pnas.1216389109

2011

Erratum: Prevention measures and exploratory pharmacological treatments of celiac disease (American Journal of Gastroenterology (2010) 105 (2551-2561) DOI: 10.1038/ ajg.2010.372)

Pinier M, Fuhrmann G, Verdu E, Leroux J (2011)

American Journal of Gastroenterology, 106 (2)DOI: 10.1038/ajg.2010.454

In vivo fluorescence imaging of exogenous enzyme activity in the gastrointestinal tract

Fuhrmann G, Leroux J (2011)

Proceedings of the National Academy of Sciences of the United States of America, 108 (22): 9032-9037DOI: 10.1073/pnas.1100285108

2010

In vitro evaluation of the stability of proline-specific endopeptidases under simulated gastrointestinal conditions

Fuhrmann G, Leroux J (2010)

J Control Release, 148 (1): 37-39DOI: 10.1016/j.jconrel.2010.07.046

Prevention measures and exploratory pharmacological treatments of celiac disease

Pinier M, Fuhrmann G, Verdu E, Leroux J (2010)

American Journal of Gastroenterology, 105 (12): 2551-2561DOI: 10.1038/ajg.2010.372

Tyrosine-based rivastigmine-loaded organogels in the treatment of Alzheimer's disease

Bastiat G, Plourde F, Motulsky A, Furtos A, Dumont Y, Quirion R, Fuhrmann G, Leroux J (2010)

Biomaterials, 31 (23): 6031-6038DOI: 10.1016/j.biomaterials.2010.04.009

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