CO releasing molecules; Targeted drug delivery; Vitamin B12; Diatoms; Bio-inspired vectors and materials ; IR imaging; Chemotherapeutic drugs
Sovari Sara Nasiri, Vojnovic Sandra, Bogojevic Sanja Skaro, Crochet Aurelien, Pavic Aleksandar, Nikodinovic-Runic Jasmina, Zobi Fabio (2020), Design, synthesis and in vivo evaluation of 3-arylcoumarin derivatives of rhenium(I) tricarbonyl complexes as potent antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA), in
European Journal of Medicinal Chemistry, 205, 112533.
Rossier Jeremie, Delasoie Joachim, Haeni Laetitia, Hauser Daniel, Rothen-Rutishauser Barbara, Zobi Fabio (2020), Cytotoxicity of Mn-based photoCORMs of ethynyl-α-diimine ligands against different cancer cell lines: The key role of CO-depleted metal fragments, in
Journal of Inorganic Biochemistry, 209, 111122.
Nasiri Sovari Sara, Zobi Fabio (2020), Recent Studies on the Antimicrobial Activity of Transition Metal Complexes of Groups 6–12, in
Chemistry, 2(2), 418-452.
Delasoie Joachim, Schiel Philippe, Vojnovic Sandra, Nikodinovic-RunicJasmina, ZobiFabio (2020), Photoactivatable Surface-Functionalized Diatom Microalgae for Colorectal Cancer Targeted Delivery and Enhanced Cytotoxicity of Anticancer Complexes, in
Pharmaceutics, 1-23.
Delasoie Joachim, ZobiFabio (2019), Natural Diatom Biosilica as Microshuttles in Drug Delivery Systems, in
Pharmaceutics, 1.
Rossier Jeremie, Nasiri Sovari Sara, Pavic Aleksandar, Vojnovic Sandra, Stringer Tameryn, Bättig Sarah, Smith Gregory S., Nikodinovic-Runic Jasmina, Zobi Fabio (2019), Antiplasmodial Activity and In Vivo Bio-Distribution of Chloroquine Molecules Released with a 4-(4-Ethynylphenyl)-Triazole Moiety from Organometallo-Cobalamins, in
Molecules, 24(12), 2310-2310.
Delasoie Joachim, Rossier Jérémie, Haeni Laetitia, Rothen-Rutishauser Barbara, Zobi Fabio (2018), Slow-targeted release of a ruthenium anticancer agent from vitamin B 12 functionalized marine diatom microalgae, in
Dalton Transactions, 47(48), 17221-17232.
Marta Jakubaszek, Jeremie Rossier, Johannes Karges, Joachim Delasoie, Bruno Goud, Gilles Gasser, Zobi Fabio, Evaluation of the Potential of Cobalamin Derivatives Bearing Ru(II) Polypyridyl Complexes as Photosensitisers for Photodynamic Therapy, in
Helvetica Chimica Acta, 1.
In this SNFS application an approach to the synthetic preparation of cobalamin-based biocompatible scaffolds for CO-releasing molecules (CORMs) and chemotherapeutic drugs delivery and the development of surface functionalized diatom frustules as bio-inspired drug delivery materials and CO-releasing materials is described. Context: A key objective of medicinal chemistry is that of selectively addressing diseased or injured cell populations while leaving healthy tissues unaffected. This goal is particularly stringent for anticancer therapeutic agents but also important for other drugs as (e.g.) CORMs. The latter are a class of pharmaceutical compounds currently widely investigated due to the documented beneficial therapeutic effects of carbon monoxide (CO). Indeed, endogenous and exogenous CO ameliorates (e.g.) experimental cardiac, lung and vascular injuries and protect against numerous inflammatory states. In these fields transition metal complexes continue to play a major role. Alongside the design and identification of new pharmacologically suitable anticancer agents and CORMs, significant intellectual and chemical research efforts are also devoted to the modification of the same with tailor-made biocompatible ligands (or scaffolds) with the aim of addressing properties required for a medical drug. Often vitamins, sugars or peptides are appended to the metal complexes, but in recent years materials such as (e.g.) mesoporous silica nanoparticles or nanoporous fibers have investigated for this purpose. Approach: Within the above-mentioned context, we have been working on the development of biocompatible-site specific metal based CORMs via conjugation of active metal carbonyl complexes to natural biomolecules with a focus on vitamin B12. Recently the same strategy was extended in our group to anticancer drugs. The validity of our approach was confirmed by very promising biological and medical data. With this prolongation proposal I intend to develop and expand the concepts above to bio-inspired vectors and materials for the targeted delivery of CO-releasing molecules and chemotherapeutic agents. In order to realize the goals of this project, the proposed research will be divided into two subprojects. These are strongly interconnected and the responsible students will work synergistically towards the common greater objective.Aims: The fundamental objectives of this research may be summarized as follows:Subproject Aa) Further develop site-specific metal-based therapeutic agents which will function as “prodrug” regulators of biological networks (hence our interest in CORMs as CO delivery prodrugs). b) Expand our current library of vitamin B12 vectors for ligand-supported CORM and chemotherapeutic drugs conjugation and delivery. Subproject Bc) Develop diatom frustules-based bio-inspired materials for targeted drug delivery. d) Improve and establish methods and protocols for the 3D tomographic reconstruction of fluorescent and IR imaging studies of drug distribution on frustules and live cells.