Dynamische DNA-Hydrogele, die durch biochemische Treibstoffe aktiviert werden
Polymermaterialien
Zusammenfassung der Projektergebnisse
DNA hybridization's programmable and reversible nature makes DNA-based nanoparticle assemblies a powerful tool for creating dynamic nanostructures with properties that evolve over time. We successfully implemented a DNA-fueled, four-dimensional Au-nanostructure assembly that autonomously self-assembles and possesses the ability to architecturally evolve into different core-satellite structures depending on the DNA sequence of the added fuel in the presence of ExoIII as the energy dissipating enzyme. This system could pave the way for creating highly complex dissipative AuNP architectures that can regulate cellular interactions without external intervention. Furthermore, it may inspire future work in designing dissipative nanoparticle systems with evolving plasmon resonance properties. Additionally, we investigated the toe-hold-dependent digestion kinetics of ExoIII and T7 exonuclease to gain precise control over the transient lifetime of a double-stranded DNAzyme and the protein-enzyme trypsin. We achieved this control not only through means of fuel and energy dissipating-enzyme concentration, but also via toe-hold length-dependent digestion kinetics of the fuel consuming enzyme. This approach only requires the introduction of small toe-holds, enabling the internal regulation of digestion kinetics without modifying the overall system. With the ever-growing number of novel aptamers that can bind and inhibit different enzymes, more biologically relevant dissipative self-assembling systems can be developed. Spatiotemporal control of enzymes is critical to understand biological processes and create artificial cell-like systems. Finally, we developed for the first time a dissipative DNA-based drug delivery system that can interact with living cells to stimulate an immune response. The system is designed to deliver pharmacologically active CpG ODNs using different types of DNA fuels. Through hybridization with the DNA fuel, the CpG ODN is inactivated, and subsequent hydrolysis of the fuel via T7 exonuclease results in the stimulation of the immune response through the interaction of the CpG ODN with the TLR9 protein. The system resulted in an even higher immune response than that of pristine CpG ODN. We also investigated how the system functions in J774A.1 mouse macrophages, which are immune cells that naturally express mTLR9. Upon activation of mTLR9, macrophages produce TNF-α, which serves as a marker of immunostimulation. The addition of T7 showed a potent immunostimulatory response, which could not be achieved with pristine CpG ODN. This may be due to the protection of CpG ODN via the hybrid system, leading to higher early-stage activity. T7 exonuclease leads to the release of the CpG ODN, making it available at higher effective concentrations at the receptor's binding site, leading to increased activity. This approach could be used to design interactive systems that use cellowned signals to trigger the release of bioactive oligomers from hybrid systems, allowing for targeted treatment of various disorders. Additionally, the approach could be used to deliver other functional ODNs.
Projektbezogene Publikationen (Auswahl)
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Four‐Dimensional Deoxyribonucleic Acid–Gold Nanoparticle Assemblies. Angewandte Chemie, 132(39), 17403-17408.
Luo, Ming; Xuan, Mingjun; Huo, Shuaidong; Fan, Jilin; Chakraborty, Gurudas; Wang, Yixi; Zhao, Hui; Herrmann, Andreas & Zheng, Lifei
