Cellular Biochemistry, Molecular Imaging and Biosensors. Coordinator: Iotti

The group's goal is the development of integrated and interdisciplinary approaches to study the molecular mechanisms that underlie the common cellular metabolic processes. This will allows to obtain an overall and organic view of cellular biochemistry.

Research themes

The research activity concerns the development and application of advanced investigation methods for the study of cellular metabolism in physiological and pathological conditions on a single cell and on cell populations and the role played by Magnesium in the modulation of the main cellular processes.

Development and use of fluorescent probes for the study of cellular metabolism of magnesium.

This research activity contemplates the design of , synthesis, characterization and application of new specific fluorescent probes for Magnesium. These probes are obtained by conjugating hydroxyquinoline derivatives to corona ethers. The synthesis of these probes has been patented. Currently, a specific probe is being developed to mark mitochondrial magnesium.

Antiproliferative and reverting Multiple Drug Resistance (MDR) activity of phytocomplexes and new synthetic molecules. This research activity aims to evaluate the antiproliferative, proapototic and reverting effects of MDR of a series of molecules, synthesized by colleagues from the Department of Pharmacy and Biotechnology, in different tumor cell lines sensitive and resistant to doxorubicin. In addition, the involvement of Magnesium in the processes of cell proliferation, in the progression through the cell cycle, in the induction of apoptosis in particular in the mitochondrion mediated pathway and in the establishment of the MDR phenotype is being evaluated.

Development of nanocarrier systems for anticancer drugs. The purpose of this research is to test the antiproliferative effects of anticancer drugs encapsulated in different delivery systems and to follow their intracellular uptake. The nanoencapsulation of drugs allows their accumulation at the tumor site avoiding an uncontrolled distribution to the various districts of the organism, both by exploiting the ability of the nanoparticle vector to 'extravasate' through the discontinuities of the tumor capillary endothelium to remain trapped only in tumor tissue which by derivatizing the nanoparticles with residues capable of binding to molecular structures overexpressed on tumor cells. For the different nanocarrier systems it is necessary to evaluate the correct release of the drug and the potency and efficacy that can be obtained.

Cell imaging with x-ray techniques generated by synchrotron light. This research activity aims to study at different levels of scale (micrometric, nanometric and atomic) the different cellular processes such as the sub-cellular compartmentalization of magnesium and other elements, the nano-structural modifications induced in cells by drug resistance and mitochondrial morphology. Furthermore, this line of research aims to study biomineralization both in the initial phases  of stem cells during osteoblastic differentiation, and in its more advanced stages in healthy and pathological (osteosarcoma and osteoporosis) human bone tissue . To achieve these goals, various X-ray techniques generated by synchrotron light such as fluorescence, 3D imaging, and diffraction are used.

Laboratory members

Prof. Stefano Iotti (Professore Ordinario)

Paolo Neyroz (Professore Associato)

Giovanna Farruggia (Ricercatore confermato)

Concettina Cappadone (Ricercatore confermato)

Emil Malucelli (Ricercatore confermato)

Giovanna Picone (Dottoranda)

Internship projects

Study of the anti-proliferative and reverting activity of the multiple resistance to drugs of phytocomplexes and new synthetic molecules.

Synthesis and characterization of new nanoparticles for drug delivery.

 3D cultures of bone cells on biocompatible materials.

2 erasmus positions (Marseille (Fr) and  Reykjavík (Is)

Significant Publications

Malucelli E, Iotti S, Gianoncelli A, Fratini M, Merolle L, Notargiacomo A, Marraccini C, Sargenti A, Cappadone C, Farruggia G, Bukreeva I, Lombardo M, Trombini C, Maier JA, Lagomarsino S (2014) Quantitative Chemical Imaging of the Intracellular Spatial Distribution of Fundamental Elements and Light Metals in Single Cells. Anal Chem 86:5108–5115. doi: 10.1021/ac5008909

Sargenti A, Farruggia G, Zaccheroni N, Marraccini C, Sgarzi M, Cappadone C, Malucelli E, Procopio A, Prodi L, Lombardo M, Iotti S (2017) Synthesis of a highly Mg2+-selective fluorescent probe and its application to quantifying and imaging total intracellular magnesium. Nat Protoc 12:461–471. doi: 10.1038/nprot.2016.183

E. Malucelli, A. Procopio, M. Fratini, A. Gianoncelli, A. Notargiacomo, L. Merolle, A. Sargenti, S. Castiglioni, C. Cappadone, G. Farruggia, M. Lombardo, S. Lagomarsino, J.A. Maier, S. Iotti (2018). Single cell versus large population analysis: cell variability in elemental intracellular concentration and distribution. Anal Bioanal Chem 410:337–348 https://doi.org/10.1007/s00216-017-0725-8

Alessandra Procopio, Emil Malucelli, Alexandra Pacureanu, Concettina Cappadone, Giovanna Farruggia,,Azzurra Sargenti, Sara Castiglioni, Davide Altamura, Andrea Sorrentino,Cinzia Giannini, Eva Pereiro, Peter Cloetens, Jeanette A. M. Maier, and Stefano Iotti (2019). Chemical Fingerprint of Zn−Hydroxyapatite in the Early Stages of Osteogenic Differentiation. ACS Cent. Sci. 5, 1449−1460.

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