Proof-of-Concept Multistage Biomimetic Liposomal DNA Origami Nanosystem for the Remote Loading of Doxorubicin

One of the most promising applications of DNA origami is its use as an excellent evolution of nanostructured intelligent systems for drug delivery, but short in vivo lifetime and immune-activation are still major challenges to overcome. On the contrary, stealth liposomes have long-circulation time and are well tolerated by the immune system. To overcome DNA origami limitations, we have designed and synthesized a compact short tube DNA origami (STDO) of approximately 30 nm in length and 10 nm in width. These STDO are highly stable ≥48 h in physiological conditions without any postsynthetic modifications. The compact size of STDO precisely fits inside a stealthy liposome of about 150 nm and could efficiently remotely load doxorubicin in liposomes (LSTDO) without a pH driven gradient. We demonstrated that this innovative drug delivery system (DDS) has an optimal tumoral release and high biocompatible profiles opening up new horizons to encapsulate many other hydrophobic drugs.