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TY  - THES
AU  - Rath, Wolfgang Hubertus
TI  - Functional nucleic acids for ultrasound-controlled release and targeted cancer theranostics
PB  - RWTH Aachen University
VL  - Dissertation
CY  - Aachen
M1  - RWTH-2025-10722
SP  - 1 Online-Ressource : Illustrationen
PY  - 2025
N1  - Veröffentlicht auf dem Publikationsserver der RWTH Aachen University 2026
N1  - Dissertation, RWTH Aachen University, 2025
AB  - This thesis explores how functional nucleic acids (FNAs) can be used to construct ultrasound-responsive release systems and theranostic applications for the diagnosis and therapy of cancer. In contrast to synthetic polymers, FNAs offer powerful sequence programmability, the ability to form defined secondary and tertiary structures and can directly interface with biological systems. Another outstanding feature of FNAs is that they can easily be chemically modified. In particular, this thesis highlights two versatile techniques that can be used to generate multifunctional NAs: rolling circle amplification and copper-free Click reaction. RCA is an isothermal amplification technique that generates polynucleotides with very large molar mass. Due to their size, RCA products can be used to construct US-responsive systems. They are also a useful tool in the context of drug delivery, since they exhibit high nuclease stability and slow renal clearance. The copper-free Click reaction is one of the most important biolabeling reactions, which can be used to functionalize NAs with a variety of labels to facilitate imaging or therapeutic applications. Chapter 1 of this thesis summarizes the necessary scientific context for this work. Firstly, the fundamentals of FNAs and their applications in the context of cancer drug delivery are summarized. The most common reactions for the chemical modification of NAs, as well as different labeling strategies for FNAs to facilitate various imaging techniques are discussed. Furthermore, the basics of polymer mechanochemistry, and how they can be applied to NAs in order to generate biocompatible mechanochemical systems are introduced. In chapter 2, a mechanoresponsive system for the US mediated activation of an RNA-cleaving DNAzyme is presented. This system is based on a large DNA strand generated through RCA, onto which the DNAzyme is hybridized to deactivate it. The DNAzyme can then be released through US and subsequently cleave its substrate which is monitored by fluorescence. Chapter 3 presents an RCA based drug delivery system for the treatment of glioblastoma using an in ovo model. For this purpose, the AS1411 aptamer sequence is encoded onto the RCA strand, providing a glioblastoma targeting function. Additionally, a chelator for radiolabeling is attached to the RCA strand through Click chemistry and the anticancer drug Doxorubicin is loaded onto the DNA via non-covalent interactions. In combination, these elements form a flexible theranostic platform for positron emission tomography using 68Ga, and the co-delivery of Dox and 177Lu for combined chemo- and radiotherapy. Chapter 4 introduces an aptamer Click labeling strategy to generate targeted contrast agents for magnetic resonance imaging. The enhancement in MRI contrast is achieved through para-hydrogen induced polarization (PHIP). When conjugated with an aptamer, these PHIP tags are promising tools for targeted cancer imaging with MRI at low magnetic fields, for example in portable MRI machines. The final section summarizes this work and gives some outlook on potential future research topics.
LB  - PUB:(DE-HGF)11
DO  - DOI:10.18154/RWTH-2025-10722
UR  - https://publications.rwth-aachen.de/record/1023760
ER  -