ABSTRACT
Over the last decade, gene therapy has undergone considerable expansion with improved knowledge of the genome and also with the discovery of siRNA. Gene therapy involves inserting a fragment of RNA or DNA into the cell that can directly/indirectly modify the expression of a target gene. Strategies consist of increasing the expression of a gene with the insertion of a new copy, or by inhibiting the expression of a gene with the insertion of siRNA. Due to renal fi ltration, nuclease degradation, and a poor cellular uptake, the encapsulation of these hydrophilic molecules is necessary to consider their use in vivo. As most nanocarriers have a predominantly hydrophobic solid or liquid core, the combination of nucleic acids with hydrophobic forms has necessitated the development of appropriate formulations. A possible association within liposomes has been largely developed: indeed, cationic lipids used for liposome formulation can react with the negative charge of nucleic acids and form stable complexes called lipoplexes. In addition, they have a good cellular uptake. Gupta et al. (2007) demonstrated this transfection ability in nude mice that received U87MG human glioma cells. An alternative form was developed by Morille et al. (2010a) and consisted of the encapsulation of lipoplexes within lipid nanocapsules. They showed long-circulating properties and accumulation by EPR effect in sub-cutaneous U87MG glioma model after intravenous injection. Moreover, examples of active targeting were realised by grafting TF or chlorotoxin. This latter agent is commonly used for labelling property, but in this case, chlorotoxin modifi ed nanoparticles showed an improved cellular uptake and high gene expression.
