Two different types of nanocarriers, lipid nanocapsules (LNC) and multimodular systems (MMS) were developed for systemic administration of two types of nucleic acids, DNA and small interfering RNA (siRNA). These nanocarriers are based on complexes between nucleic acids and cationic lipids (lipoplexes) which were either encapsulated in LNC or coated with steric stabilizers to form MMS. One part of this work consisted in the development of siRNA nanocarriers and in their characterisation using physico-chemical methods. In function of the cationic lipid, up to 65% of siRNA could be encapsulated in LNC and presented appropriate characteristics for systemic administration. The second part consisted in the advanced characterisation of DNA nanocarriers and the analyse of their biodistribution profiles using in vivo biofluorescence imaging. In healthy animals, the different DNA nanocarriers presented various distribution profiles in function of their composition. On two tumour mouse models (glioma and melanoma), the DNA nanocarriers presenting a prolonged circulation time showed also colocalisation with tumour cells. To evidence their efficacy, a plasmid coding for herpes simplex virus thymidine kinase (HSV-tk) was encapsulated and administered, followed by a treatment of ganciclovir (GCV) using the gene-directed enzyme prodrug therapy. The first results are promising, and showed a tumour growth reduction after several days compared to non-treated animals. In conclusion, the results suggest that these nanocarriers could present a promising tool for various applications in gene therapy.
