Metallodrugs and metallo-enzymes

Transition metal catalysis and biocatalysis have been the most widely used approaches to producing enantiopure products. These synthetic methods have been considered as separate fields until recently, when artificial metalloenzymes (Ar – Ms) have emerged, combining the attractive properties of both approaches.

In order to achieve this goal , the supramolecular anchoring strategy results particularly convenient with the biotin – (strept)avidin technology proving the most representative anchoring system in this field .

Based on biotin – streptavidin bioconjugation , we have recently developed a series of artificial imine reductase in which a chiral biotinylated 1,3 – diamine ligand or a biotin – tethered Cp* moiety was coordinated with an iridium(III) centre and anchored to a streptavidin mutant for the stereoselective reduction of the cyclic imines.

Inspired by the recently reported ability of the glycopeptide vancomycin (Van) to coordinate bivalent metal ions and encouraged by the results obtained by using Van for setti ng up a hybrid catalyst in coordination to an iridium centre , vancomycin was exploited as a new chiral second coordination sphere for the preparation of artificial metalloenzymes in the presence of aminoethylbenzensulfonamide ligands decorated with the D – A la – D – Ala dimer .

These hybrid systems have the potential to impact chemical synthesis in ways not readily achiev able using conventional transition metal catalysts . The concept of using modern medicinal chemistry approaches to investigate the structure and properties of metal complexes for medicinal purposes has matured immensely in the 50 years since the Rosenberg discovery of cisplatin.

The persistence of severe sid e – effects along with the emerging of drug resistance evoke the need of a new generation of transition metal – based chemotherapeutics.These premises guided our research group in the development of new platinum complexes not only neutral but also positively and negatively charged .

Indeed, different chelating diamine ligands have been developed base on aminomethyl imidazole and 8 – amino quinoline scaffolds with the idea to provide a novel pharmacodynamic profile to the corresponding platinum complexes

Using the rheometer present within our laboratory, we can study and design many parameters and properties such as the kinetics of gel formation, the frequency sweep, the amplitude sweep, and much more.

Combining the expertise of the group, different nanomaterials can be crosslinked into the polymeric network, to enhance the properties of the soft materialThe aim of this research thrust is to imbue advanced functions onto materials by creat ing hybrids through the incorporation of silica nanoparticles into the overall design strategy.

Some of t hese tailorable fun ct ions include on – demand degradability, release of payloads, tuning of hydrogel gelation and material properties, biocompatibility, and directed cell growth.

Future studies look to expand on our previous work by capitalizing on the numerous uniquely dynami c properties of silica nanoparticles that can be exploited when incorporated into hydrogels and other scaffold materials to pioneer cutting – edge hybrid nanomaterials

Selected Publications:

Piantanida E, Boškoski I, Quero G, Gallo C, Zhang Y, Fiorillo C, Arena V, Costamagna G, Perretta S, De Cola L. Nanocomposite hyaluronic acid – based hydrogel for the treatment of esophageal fistulas.

Materials Today Bio. 2021 Mar 1;10:100109 Piantanida E, Alonci G, Bertucci A, De Cola L. Design of nanocomposite injecta ble hydrogels for minimally invasive surgery.

Accounts of chemical research. 2019 Jul 10;52(8):2101 – 12. Alonci G, Fiorini F, Riva P, Monroy F, López – Montero I, Perretta S, De Cola L. Injectable hybrid hydrogels, with cell – responsive degradation, for tumor resection.

ACS Applied Bio Materials. 2018 Oct 19;1(5):1301 – 10. Fiorini F, Prasetyanto EA, Taraballi F, Pandolfi L, Monroy F, López ‐ Montero I, Tasciotti E, De Cola L. Nanocomposite hydrogels as platform for cells growth, proliferation, and chemotaxis. Smal l. 2016 Sep;12(35):4881 – 93.

Porous nanosystems for targeted drug delivery

The main research thread in our group is the development of porous nanocarriers characterized by high biocompatibility, degradability, large surface area for drug loading, stability and low costs. Moreover, many properties of these nanomaterials can be finely tuned, depending on the final application.Zeolites, organosilica nanoparticles, silicon nanoparticles, and mesoporous silica, represent the most studied nanosystems in our group. Depending on their structure, these materials can entrap either small or large therapeutic or imaging biomolecules. Noteworthily, they can even break with an external stimulus in the target tissues/cells.Such nanosystems can exhibit different morphologies, dimensions, and structures. Their physico-chemical properties can be conveniently tailored by functionalizing their surface with a wide plethora of functional groups. Part of our efforts are also focused on the synthesis of microporous materials to construct artificial receptors for selectively capture hydrophilic molecules present in biological fluids, both for diagnostic and treatment purposes.Our objective is to design smart novel micro- and nanomaterials with a potential translation into the clinical practice, and with a broad range of properties for in vitro and in vivo applications, such as diagnostics and therapy for several disease.