Development of fluorinated biodegradable cationic nanoparticles for imaging and gene delivery

This work represents a study on the synthesis and characterization of fluorinated cationic PEGylated polymers as a novel alternative to currently used gene delivery carriers in gene therapy and contrast agents. These nanoparticles possess features such as biodegradability, functionalization with fluorine to exploit the low concentration of this atom inside the human body (making them suitable contrast agents in 19F-NMR), a cationic core to enhance interaction with genetic cargo, and PEGylation to improve biocompatibility and reduce immune response. In the first part of the thesis, each component was synthesized. The cationic lipophilic core was obtained through Ring Opening Polymerization (ROP), where a set number of lactone chains (namely ε-caprolactone) were added to a tertiary amine alcohol, dimethylethanolamine (Deanol). The surfactant block, composed of both functionalized and non-functionalized PEG chains, was obtained via RAFT polymerization in the following way: first, PEG was acylated to add CF3 groups to its terminal end (PEG-CF3). Then, the PEG-CF3 was used as a building unit to obtain two separate fluorinated blocks containing five and fifteen chains of fluorinated PEG. To this block, a set number of non-functionalized PEG chains were added through RAFT polymerization to obtain a total number of surfactant chains equal to fifty. The final step of the synthesis employed PISA polymerization to obtain polymeric fluorinated nanotracers viable as contrast agents in 19F-NMR, with variable core size and composition. The nanoparticles thus obtained were analyzed in terms of size and surface charge, both with and without genetic cargo. The size of the nanoparticles without the genetic cargo was acceptable, and the surface charge was neutral, making them suitable for the contrast agent application, taking into account the optimal visibility of fluorine peak in D2O in 19F-NMR analysis. However, once loaded with genetic material, each nanoparticle exhibited an increase in size, making them unsuitable as gene carriers.