SFB 1278:  Polymer-based nanoparticle libraries for targeted anti-inflammatory strategies

• Subject Area: Chemistry ; Biology ; Medicine ; Physics
• Term: since 2017
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 316213987

The fight against inflammatory diseases, for example induced by infections, is of great importance for mankind and requires novel strategies for effective and safe pharmacotherapy. Current concepts for medication of inflammatory diseases suffer from restricted biocompatibility and organ specificity of available drugs and are associated with severe side effects. The CRC POLYTARGET offers innovative approaches for solving these treatment hurdles. Our consortium pursues the long-term goal to develop cell type-specific polymeric nanoparticle (NP) carriers for selective interference at different stages of the inflammatory processes. Targets for NP treatment include pathogens directly or concomitant harmful inflammatory reactions. Newly developed drugs encapsulated by tissue-specific NPs allow to resolve local and systemic inflammatory responses and protect remote organs. Based on these strategies POLYTARGET addresses a broad spectrum of inflammatory diseases leading to organ failures, i.e., sepsis. To face these challenges, a holistic view of the causes and effects of inflammatory reactions is required. POLYTARGET maps the entire range of methods for generation and efficient application of cell type-specific NPs, which covers the synthesis of systematic polymer libraries, the formulation of NP libraries, the development of new anti-inflammatory drugs, modelling of drug-polymer interactions and the implementation of biomedical evaluation methods for testing the efficacy of drug-loaded NPs. The CRC's particular strength is the ability to comprehensively characterize all steps involved in the generation and implementation of the NPs. Area A – CORE hosts the projects that deal with the “interior” of the NPs in a broad sense. Projects in Area B – SHELL focus on the surface-related effects of NPs on biomolecules and cells. Area C – MEDIUM expands the research level and includes cells, organisms, organoids and animal experiments. Area D – VIRAL exploits the CRC`s expertise for fighting viral infections, and a public outreach project (Ö01) translates the concepts and findings of POLYTARGET to school education. The underlying Area Z supplies the whole CRC with key technologies including chemical synthesis, upscaling, supply of human macrophages, central analytical techniques as well as bioinformatics approaches, but also with the scientific claim to further develop these methods. Moreover, the POLYTARGET Research Training Group (RTG) will continue educational mentoring of PhD researchers associated to the CRC by promoting their interdisciplinary scientific expertise to optimise the conditions for research and personal development.

• DFG Programme: Collaborative Research Centres

Current projects

• A01 - Tailor-made multifunctional polymers and nanoparticles with optimised compatibility between biodegradable core and encapsulated drug (Project Heads Schubert, Ulrich S. ;  Sierka, Marek )
• A02 - Multifunctional nanoparticles based on polysaccharides for targeted drug delivery with two-step release behavior (Project Heads Coldewey, Ph.D., Sina Maren ;  Heinze, Thomas ;  Heinzel, Thorsten )
• A03 - Photoacids and bases as responsive elements in block copolymer nanostructures for uptake and transport (Project Heads Dietzek-Ivansic, Benjamin ;  Jandt, Klaus D. ;  Schacher, Felix H. )
• A04 - Spatial and temporal targeting of membrane-bound mPGES-1 and FLAP / 5-LO by dual inhibitors employing polymer-based nanocarriers (Project Heads Eggeling, Christian ;  Schubert, Ulrich S. ;  Werz, Oliver )
• A05 - Targetable nanoparticles for efficient translocation across gastrointestinal barriers (Project Heads Brendel, Johannes ;  Mosig, Alexander ;  Stallmach, Andreas )
• A06 - Controlling stealth and barrier breaking behavior: Hybrid protein nanofibers and POxylation on polymeric nanoparticles with structurally tailored thermal properties (Project Heads Jandt, Klaus D. ;  Schubert, Ulrich S. )
• B01 - Multicomponent nanoparticles for efficient targeting of inflammatory signaling and memory in hematopoietic stem and myeloid cells (Project Heads Rudolph, Karl Lenhard ;  Träger, Anja )
• B02 - Macromolecular prodrug nanoparticles for antimicrobial therapy (Project Heads Brakhage, Axel ;  Guerrero Sanchez, Ph.D., Carlos Antioco )
• B03 - Bioinspired guanidinium-containing nanoparticles for gene delivery (Project Heads Fischer, Dagmar ;  Peneva, Ph.D., Kalina )
• B04 - Nanoscale monitoring of surface effects, structural changes, and encapsulation in block copolymer nanostructures using tip-enhanced Raman spectroscopy (Project Heads Deckert, Volker ;  Schacher, Felix H. )
• B07 - Quantitative single-molecule characterization of cytosolic nanoparticle cargo release by multi-colour, threedimensional dSTORM (Project Head Franke, Christian )
• B08 - The mechanism and the immunomodulatory consequences of protein adsorption on stealth nanoparticles (Project Heads Hellmich, Ute ;  Press, Adrian )
• C01 - Biophotonic characterisation of the interaction of nanoparticles and drugs with hepatic stellate cells (Project Heads Bauer, Michael ;  Popp, Jürgen ;  Schubert, Stephanie )
• C02 - Tailored delivery of anti-inflammatory natural drugs using polymer-based nanocarriers to prevent cytokine and eicosanoid storms in infectious inflammation (Project Heads Fischer, Dagmar ;  Werz, Oliver )
• C04 - Investigation of cellular response to nanoparticle uptake by dual TEM and superresolution fluorescence imaging (Project Heads Heintzmann, Rainer ;  Höppener, Stephanie )
• C06 - Prevention of late phase liver damage by targeted modulation of the liver’s immune response (Project Heads Bauer, Michael ;  Schubert, Ulrich S. ;  Waskow, Claudia )
• D01 - Mimicking viral entry mechanisms with polymeric nanoparticles (Project Heads Bauer, Michael ;  Eggeling, Christian ;  Schubert, Ulrich S. )
• D02 - Delivery platforms for antiviral and anti-inflammatory agents targeting infections of respiratory viruses with pandemic potential (Project Heads Ehrhardt, Christina ;  Hoffmann, Carsten ;  Löffler, Bettina ;  Schubert, Stephanie )
• T01 - Targeting renal phosphoinositide 3-kinase γ (PI3Kγ) by dye-tagged nanoparticles (Project Heads Bauer, Michael ;  Coldewey, Ph.D., Sina Maren ;  Schubert, Ulrich S. )
• Z01 - Research platform for the synthesis, formulation, and advanced physicochemical characterisation of polymers and nanoparticles (Project Heads Eggeling, Christian ;  Figge, Marc Thilo ;  Guerrero Sanchez, Ph.D., Carlos Antioco ;  Höppener, Stephanie ;  Lorkowski, Stefan ;  Nischang, Ivo )
• Z02 - Integrated Research Training Group (Project Heads Dietzek-Ivansic, Benjamin ;  Schubert, Stephanie ;  Werz, Oliver )
• Z03 - Central tasks of the Collaborative Research Center (Project Head Schubert, Ulrich S. )
• Ö01 - Science education on target: Didactic reconstruction of current research at the interface between nanotechnology and medicine (Project Head Wilke, Timm )

Completed projects

• B06 - Targeted nanoparticle mediated delivery of nucleic acids into muscle stem cells for prevention of critical illness myopathy (Project Head Träger, Anja )
• C03 - Selective targeting of hepatocytes using multifunctional block copolymer micelles to restore critical cellular signaling functions (Project Heads Bauer, Michael ;  Qualmann, Britta ;  Schacher, Felix H. )
• C05 - Advanced fluorescence microscopy investigations of lipid-membrane nanoparticle interactions (Project Head Eggeling, Christian )

• Applicant Institution: Friedrich-Schiller-Universität Jena
• Participating University: Friedrich-Alexander-Universität Erlangen-Nürnberg
• Participating Institution: Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI); Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V.; Hans-Knöll-Institut (HKI); Leibniz-Institut für Photonische Technologien e.V. (IPHT); Universitätsklinikum Jena
• Spokesperson: Professor Dr. Ulrich S. Schubert