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.
