Carbon Dots for siRNA delivery and PDT: Application to atopic dermatitis – CaDoRNA

Atopic dermatitis (AD) is a common inflammatory skin disease, often of early-life onset, for which the prevalence continues to increase in industrialized countries, affecting approximately 15-30% of children and 2-10% of adult. AD remains challenging to treat, therefore the CadoRNA project is designed to conduct proof-of-concept study aiming at establishing a light activated nucleic acid-based therapy that is non-invasive (topical treatment), controllable (light inducible), with the advantages of easy design for identified molecular targets (nuclear acid-based) thus suitable for precision medicine. Research in the field of nucleic acid-based therapy aims at developing efficient and safe delivery systems to transfer therapeutic genetic material into the target tissues. Therefore, synthetic carriers have attracted much attention from chemists and despite remarkable progress they still require improvements for translation into the clinic. The development of new and effective siRNA delivery system is, therefore, extremely urgent. siRNA-based therapies have recently been applied to atopic dermatitis (AD), this immune disease that causes itching, drying and inflammation. On the other hand, we will explore the effect of photodynamic therapy (PDT) for the treatment of AD too. In this proposal, we wish to develop a yet unexplored approach for the treatment of AD that combines therapeutic siRNA and PDT. Delivery of siRNA will be site-specifically triggered by photoirradiation (with red or IR light) of complexes with a ROS-responsive cationic carbon dot-based carrier, while generated ROS will concomitantly 1-improve release of endocytosed material into the cytoplasmic matrix through specific chemical bond cleavages inducing siRNA decomplexation and a photochemical internalization (PCI) process and 2-exert an immunomodulatory effect. The efficiency of our small interfering RNA delivery systems coupled to PDT will be tested in a mouse model of AD.