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.

Cyclic Ketoximes as Estrogen Receptorâ€ ß Selective Agonists.

The development of estrogen receptorâ€…ß (ERß)-selective agonists represents a therapeutic strategy against several kinds of cancers, but the high homology between the two receptor subtypes, ERα and ERß, makes the achievement of this goal very challenging. In the past, we developed salicylaldoxime- and salicylketoxime-based molecules that proved to bind well to ERß. In this paper, further structural evolution of the salicylketoximes is presented: two of the newly synthesized five-membered cyclic ketoximes bind with nanomolar affinities to ERß, and they show selectivity for this subtype over ERα. Their agonist character was confirmed by cell-free coactivator recruitment assays, in which we demonstrated the ability of these compounds to form an active complex with ERß capable of recruiting coactivator proteins; this indicated their efficacy as agonists. Finally, their potency and selectivity for ERß binding were rationalized by molecular-modeling studies.

Biocompatible tailored zirconia mesoporous nanoparticles with high surface area for theranostic applications.

Nanocarriers as theranostic agents are under the spotlight in modern nanomedicine, and mesoporous nanomaterials represent a class of devices of major interest. Zirconia is biocompatible, inert with good mechanical and thermal properties for in vivo biomedical applications. Although a few examples of zirconia nanoparticles have been described, a major limitation was the low surface area, which is fundamental for payload transport. Here, a simple and highly efficient method is described for the synthesis of spherical mesoporous zirconia nanoparticles (MZNs) with a high surface area through a neutral surfactant-assisted sol-gel method. The combination of alkali halides and vacuum extraction allowed stabilization of the shape and size of MZNs and to avoid porous network failure, respectively. In comparison to published synthesis procedures, a high surface area has been obtained. Biological experiments demonstrated that MZNs were biocompatible, cell permeable and degradable providing a proof of concept for theranostic applications. A comparison with the properties of mesoporous silica nanoparticles has also been performed.