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DNA Block Copolymers: New Architectures and Applications

Final Report Summary - NUCLEOPOLY (DNA Block Copolymers: New Architectures and Applications)

We live in a world full of synthetic materials, and the development of new technologies builds on the design and synthesis of new chemical structures, such as polymers. Synthetic macromolecules have changed the world and currently play a major role in all aspects of daily life. Due to their tailorable properties, these materials have fueled the invention of new techniques and goods, from the yogurt cup to the car seat belts. To fulfill the requirements of modern life, polymers and their composites have become increasingly complex. One strategy for altering polymer properties is to combine different polymer segments within one polymer, known as block copolymers. The microphase separation of the individual polymer components and the resulting formation of well defined nanosized domains provide a broad range of new materials with various properties. Block copolymers facilitated the development of innovative concepts in the fields of drug delivery, nanomedicine, organic electronics, and nanoscience. Block copolymers do not exclusively consist of organic polymers, but researchers are increasingly interested in materials that combine synthetic materials and biomacromolecules. In the NUCLEOPOLY project we have explored nucleic acid-polymer hybrids, known as DNA block copolymers (DBCs). DNA as a polymer block provides several advantages over other biopolymers. The availability of automated synthesis offers DNA segments with nucleotide precision, which facilitates the fabrication of hybrid materials with monodisperse biopolymer blocks. The directed functionalization of modified single-stranded DNA by Watson-Crick base-pairing is another key feature of DNA block copolymers to fabricate complex architectures. Furthermore, the appropriate selection of DNA sequence and organic polymer gives control over the material properties and their self-assembly into supramolecular structures. The introduction of a hydrophobic polymer into DBCs in aqueous solution leads to soft nanoparticle structures with a hydrophobic polymer core and a DNA corona. In this project, DBC nanoparticles were investigated for the purpose of drug delivery. Therefore, different aggregates were fabricated. Amphiphilic DBCs were mixed with other amphiphilic block polymers to form mixed micelles with a stealth corona that probably allows escape of the systems from detection by the immune system. For rendering the DBC carrier system more stable the DBC nanoparticles were encapsulated by a protein shell. In this way, drugs based on nucleic acids might be more stable when administered. Moreover, drugs and imaging reagents can be loaded as well in these nanocontainers. Besides these in vitro studies, we successfully employed DNA nanoparticles for ophthalmic drug delivery in vivo. Eye drops as they are used today are often ineffective since blinking and tear fluid wash out the active pharmaceutical ingredient. Our DNA nanoparticles adhere to the ocular surface and therewith extend the resident time of the drug on the eye. In this project, it was demonstrated in animal experiments that the long survival time of the drug can be translated into a better therapeutic effect compared to conventional eye drop treatment for eye infections. Besides their use in biomedicine, DNA hybrid materials were employed for diagnostic assays. Fluorescent dyes and catalysts were combined with nucleic acids to detect DNA with high sensitivity. Moreover, DBCs were successfully integrated into nanoelectronic devices like silicon nanowire field effect transistors (FETs) for the detection of DNA.