Nolli, Maria Grazia (2025) DNA on Demand: Oligonucleotide Probes for Therapy, Diagnosis and New Materials. [Tesi di dottorato]

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Abstract

The main aim of this PhD research focuses on monitoring biomarkers that indicate different diseases to enhance public health outcomes through better early detection methods and enhanced treatment approaches. As a result, this doctoral project is essentially based on two fundamental objectives: The first objective involved developing nano- or micro-platforms to be combined with modified oligonucleotides for use in the diagnostic and therapeutic fields. In particular, a new one-pot passivation/functionalization method was created to stabilize and simultaneously decorate porous silicon, the advantageous material that was chosen for this project. This method has been developed both for the functionalization of nanoparticles with a peracetylated sugar, to exploit sugar coatings in the field of drug delivery. It has also been applied to covalently conjugate a truncated peptide nucleic acid (PNA) probe on a chip for the design of a biosensor useful for diagnosing myocardial infarction. The second objective focused on the creation of DNA-based supramolecular structures for diagnostic purposes, starting from small lipophilic oligonucleotides used as building blocks. Moreover, it included the study of the modulation of the G-quadruplex structures involved in gene regulation by putative ligands. This research combines chemical synthesis with nanotechnology and nucleic acid engineering to develop adaptable platforms for precision medicine applications, which include advanced diagnostics, drug delivery, and gene regulation systems.

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