Engineered DNA nanostructures for targeted breast cancer therapy

In this work, I am presenting my PhD project accomplished during three years in nanotechnology. In this dissertation, we address the challenge of developing a drug delivery system based on DNA nanotechnology effective at preclinical stage on breast cancer (BC). In the last decades, DNA has drawn attention of many research groups as a smart nanomaterial. High stability, easy custom synthesis, mechanical rigidity and high loading efficiency are strong suitable properties of DNA to setup a drug delivery system. Unfortunately, the application of DNA nanotechnology in vivo is limited. Once in the bloodstream, DNA is fastly recognized as exogenous material by the immune system and DNAse that favors its rapid degradation. To answer this challenge, we developed a new DDS based on short tube DNA origami (STDO) of 30 nm in length, precisely designed to fit inside pegylated liposomes (LSTDO). This hybrid system combines the properties of stealth liposome to freely circulate in the blood stream and DNA origami to interact with doxorubicin, an anthracycline utilized in the treatment of BC. In vitro and in vivo antitumor efficacy of LSTDOdoxo was assessed showing an effective improvement of the therapeutic index of doxorubicin. In particular, the LSTDOdoxo accumulates in the tumor taking advantage from the EPR effect and reduces the tumor burden. It was also demonstrated that the encapsulation of DNA origami inside pegylated liposomes allowed us to develop a safe drug delivery system, which avoid the immune response induced by the administration of exogenous DNA.