Tailored nanogels by precipitation polymerization to open the therapeutic Window of gene delivery

Abstract

Gene therapy holds immense promise as a revolutionary approach in medicine, offering the potential to treat and cure a wide range of genetic and acquired diseases. To achieve transfection of therapeutic genetic materials in targeted cells, viral and non-viral carriers have been developed. While viral vectors initially opened new avenues, their potential to activate the immune system have been unveiled during unfortunate clinical trials. In that context, nanogels have shown great advantages over other non-viral vectors for their stability, tunability, encapsulation capacity, and responsive behavior.In this thesis, we have designed temperature-responsive nanogels with a high level of control in the location of positive charges. We synthesized three very distinct structures via precipitation polymerization. The first structure presents a homogeneous distribution of positive charges in the nanogels and serve as a reference. In the two other structures, the positive charges are restricted to the core of the nanogels respectively by chemical and physical interactions. The thermo-responsive behavior permits a tuning of the positive charge availability on the surface of the nanogels. Finally, the cytotoxicity of the NGs, along with the gene loading and release performance were evaluated. The NGs showed high biocompatibility but limited transfection ability.