Initially funded by the Carl Zeiss Foundation, our junior research group (Jena Center for Soft Matter (JCSM)) was installed in 2013. It is currently funded as an interdisciplinary BMBF junior research group (NanoMatFutur, project: PolyBioMik) at the JCSM.
We focus on the potential of complex polymeric nanostructures such as micelles, nanogels, and compartmentalized particles for gene transfer in eukaryotic cells. The characterization of polymers assembled nanocarriers and biological processes provides our basis for identifying structure-property relationships.
The controlled transport of genetic material or proteins in eukaryotic cells is essential for the development of new therapeutics. Cationic polymers are able to complex the negatively charged nucleic acids to promote cell uptake by electrostatic interactions. When taken up by endosomal processes, the complexes must reach their site of action, the cytoplasm or the cell nuclei. Therefore, the endosomal membrane, an important intracellular hurdle, must be crossed. Here we develop polymers in which different strategies for successful gene transfer by efficient endosomal release mechanisms are used: (I) Polymeric micelles of block copolymers, (II) pH-independent and dependent amine functionalities, (III) integration of hydrophobic units into the polymers.
The developed gene carrier are inspired by mechanisms of nature, for example functional groups or structures used by viruses or bacteria. Interdisciplinarity is therefore the focus and is actively lived in our group. Regarding the polymers, we are currently focusing on block copolymers that have different functionalities in the side chains and polymer ends. These polymer structures can assemble into certain defined structures. By this approach, we have been able to increase the efficiency of polymers. We are also investigating the influence of certain functional groups known from nature and present in viral proteins.
Fokusing on the development of gene carrier for in vivo applications, the delivery to the targeted cell or organ shouis addressed. Therefore, we use so-called target structures that can be coupled to the polymers. Suitable molecules for this purpose are, for example, DY-635, which is a liver-specific dye specifically interacting with the organic anion transporters of the liver (e.g. OATP1B1). With this strategy different drugs can be delivered (further development by SmartDyeLiery GmbH). Nutrients such as fructose can also be used as a targeting unit and, coupled to cationic polymers, could transport genetic material into the triple-negative breast cancer cell line MDA-MB 231.
The blood-brain barrier is known for its restrictive selection and is considered one of the most difficult barriers to overcome in vivo. We were able to couple glutathione (GSH) to polymers, resulting in a significantly improved transfer of genetic material across a modelled barrier in the chip model.
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