Polymer-modified oligonucleotide sequences. towards biologically active self-assembled interfaces

This research work describes the development of new smart, biologically active materials which could be of interest, among others, to the technology of drug delivery. Amphiphilic self-assembling copolymeric systems based on oligonucleotides were designed, synthesized and characterized. In Chapter 1 (Introduction), the need for new smart materials is briefly discussed, as well as the characteristics of polymeric and copolymeric materials, and oligonucleotides and oligonucleotide-based materials. The scope of the work is also described. Chapter 2 (Synthesis) discusses the synthesis and the chemical and physico-chemical properties of the oligonucleotides and polymers used in the project. Two different synthetic approaches were developed for the synthesis of the oligonucleotide-based copolymers based on those properties, and the synthesized copolymers were chemically characterized. In Chapter 3 (Self-Assembly), after synthesis of the polymer-modified oligonucleotides, the study of their self-assembly in aqueous solution is described. These studies had the objective of characterizing the self-assembled structures and understanding the influence of the oligonucleotides on the morphological properties of the self-assembled copolymers, as well as the responsiveness of these structures to environmental stimuli. Chapter 4 (Biological Activity) deals with the preliminary studies regarding the conformation of the polymer-modified oligonucleotides and their specific interaction with their complementary nucleotide strands were carried out. Biological assays were also performed in order to study the toxicity and the internalization capability of the self-assembled polymer-modified oligonucleotides. In Chapter 5 (Conclusion and Outlook), the obtained results are summarized and further investigations are suggested in order to better understand and optimize the oligonucleotide-based copolymeric systems. Finally, Chapter 6 (Materials and Methods) describes the experimental methodology used in this work.