Molecular Biotechnology Center
Daniela Delli Castelli - PI
Associate Professor
Claudia Quattrociocchi postgraduate fellow
Giulia Vassallo PhD
Research activity
Molecular Imaging is a cutting-edge medical technique that enables the visualization and analysis of biological processes at molecular and cellular levels within living organisms. The main imaging technologies that are used to this purpose, at clinical or preclinical level, are: positron emission tomography (PET), single-photon emission computed tomography (SPECT), optical Imaging (OI), computed tomography (CT) and magnetic resonance imaging (MRI). Molecular Imaging approach holds immense promise in various fields, including oncology, neurology, cardiology, and immunology, as it provides insights into disease progression, early detection, and treatment response assessment. The combination of advanced imaging technologies with targeted molecular probes empowers scientists to unravel the intricacies of complex biological processes, leading to enhanced diagnostic accuracy and to the development of personalized therapeutic strategies. The research activity of Prof. Delli Castelli and her team belong to this area of research. In particular, in the last years, they have contributed to the advancement of research in the field of contrast agents for Magnetic Resonance Imaging for molecular targeting and metabolic imaging applications. Within the array of magnetic resonance imaging contrast agents, this group has specialized in advancing a relatively emerging category referred to as Chemical Exchange Saturation Transfer (CEST) contrast agents. The distinctiveness of these contrast agents, as opposed to conventional gadolinium-based ones, lies in their capability to simultaneously visualize multiple entities within a single image. Such implementation cannot be achieved in MRI using conventional gadolinium-based agents since the response these molecules induce in the system is undistinguishable from one molecule to another. Another distinct characteristic of this category of contrast agents, as opposed to conventional ones, is that CEST contrast can be easily modulated through tissue microenvironment parameters. Consequently, these molecules have proven to be excellent reporters of temperature, pH, redox potential, and catalytic activity. Despite these significant potentials, CEST contrast agents suffer from low sensitivity, a characteristic that the scientific community involved in their development has constantly addressed. One of the primary contribution of this research team regarding the sensitivity issue has focused on the development of nanosystems. These nanosystems, called LipoCEST have led to a remarkable increase in sensitivity by several orders of magnitude. This advancement has shifted the detection thresholds from millimolar concentrations to nanomolar concentrations, which are much more aligned with the purposes of molecular imaging. Due to the exceptional versatility of LipoCEST, these nanovesicles can be readily customized with molecular targeting vectors. Furthermore, these systems have been engineered to align themselves in a magnetic field accordingly with the sign of the magnetic susceptibility of their membrane thus altering the chemical shift (DLIPO) of the mobile protons connected to these systems. This innovation facilitates the establishment of a library for multifaceted visualization. Regarding applications in metabolic imaging, the contribution of this research team has predominantly revolved around the advancement of pH-responsive probes, particularly involving paramagnetic molecules (ParaCEST agents). In parallel with the research in the CEST feld, this team has recently exploited their expertise in nanosystems to contribute to in vitro diagnostic test development. The reporting systems for ligand/anti ligand assays based on pH variations that was designed by this team have shown a strong competitive edge, particularly in cost effectiveness, when compared to the ELISA counterparts.
At the moment, this research team is focusing its attention on the development of heteronuclear CEST agents. Utilizing hetero nuclei could lead to a reduction in sensitivity threshold; however, it might come at the cost of compromising spatial resolution. This represents a groundbreaking initiative that has not been attempted before, paving the way for an entirely novel field of research. The goal is to optimize the parameters of heteronuclear CEST to expand the boundaries of diagnostic potential in CEST-MRI. The primary focus of our efforts will be directed towards the development of probes and pulse sequences, all aimed at successfully attaining this particular objective.
2019 Horizon 2020 project “GLINT: GlucoCEST Imaging in Neoplastic Tumours”
2021-FISR2020 Fondo integrativo speciale per la ricerca istituito dal Ministero dell’Istruzione dell’Università e della Ricerca “Test Covid-19 basato su turbidimetria”
2023 Proof of Concept (PoC) – TOINPROVE/2023 “Composizione di liposomi e metodo di dosaggio basato sull’uso degli stessi”
Vassallo, Giulia, Garello, Francesca, Aime, Silvio, Terreno, Enzo, Delli Castelli, Daniela* (2022). 31P ParaCEST: 31P MRI-CEST Imaging Based on the Formation of a Ternary Adduct between Inorganic Phosphate and Eu-DO3A. INORGANIC CHEMISTRY, vol. 61, p. 19663-19667, ISSN: 0020-1669, doi: 10.1021/acs. inorgchem.2c03329
Tripepi, Martina, Bennardi, Paolo O., Ferrauto, Giuseppe, Aime, Silvio, Delli Castelli, Daniela* (2021). LipHosomes: Reporters for Ligand/Anti-Ligand Assays Based On pH Readout. ANALYSIS & SENSING, vol. 1, p. 48-53, ISSN: 2629-2742, doi: 10.1002/anse.202000001
Ferrauto G., Tripepi M., Di Gregorio E., Bitonto V., Aime S., Delli Castelli D.* (2021). Detection of U-87 Tumor Cells by RGD-Functionalized/Gd-Containing Giant Unilamellar Vesicles in Magnetization Transfer Contrast Magnetic Resonance Images. INVESTIGATIVE RADIOLOGY, vol. 56, p. 301-312, ISSN: 0020-9996, doi: 10.1097/RLI.00000000000007425 2020
Tripepi M., Ferrauto G., Bennardi P. O., Aime S., Delli Castelli D.* (2020). Multilamellar LipoCEST Agents Obtained from Osmotic Shrinkage of Para Magnetically Loaded Giant Unilamellar Vesicles (GUVs). ANGEWANDTE CHEMIE. INTERNATIONAL EDITION, vol. 59, p. 2279-2283, ISSN: 1433- 7851, doi: 10.1002/ anie.201912327
Ferrauto, Giuseppe, Beauprez, Frederik, Di Gregorio, Enza, Carrera, Carla, Aime, Silvio, Terreno, Enzo, Delli Castelli, Daniela* (2019). Development and characterization of lanthanide-HPDO3A-C16-based micelles as CEST-MRI contrast agents. DALTON TRANSACTIONS, vol. 48, p. 5343-5351-5351, ISSN: 1477-9226, doi: 10.1039/c8dt04621b 6 2019
Dastrù, Walter, Menchise, Valeria, Ferrauto, Giuseppe, Fabretto, Serena, Carrera, Carla, Terreno, Enzo, Aime, Silvio, Delli Castelli, Daniela * (2018). Modulation of the Prototropic Exchange Rate in pH-Responsive Yb-HPDO3A Derivatives as ParaCEST Agents. CHEMISTRYSELECT, vol. 3, p. 6035-6041, ISSN: 2365- 6549, doi: 10.1002/slct.201800283 Delli Castelli Daniela, Tei Lorenzo, Carniato Fabio, Aime Silvio, Botta Mauro (2018). [Yb(AAZTA)(H2O)]−: an unconventional ParaCEST MRI probe.. CHEMICAL COMMUNICATIONS, p. 2004-2007, ISSN: 1364-548X, doi: 10.1039/c8cc00193f
Delli Castelli, Daniela, Ferrauto, Giuseppe, Di Gregorio, Enza, Terreno, Enzo, Aime, Silvio (2015). Sensitive MRI detection of internalized T1 contrast agents using magnetization transfer contrast. NMR IN BIOMEDICINE, vol. 28, p. 1663-1670, ISSN: 0952-3480, doi: 10.1002/nbm.3423
Garello, Francesca, Stefania, Rachele, Aime, Silvio, Terreno, Enzo, Delli Castelli, Daniela* (2014). Successful entrapping of liposomes in glucan particles: An innovative micron-sized carrier to deliver water-soluble molecules. MOLECULAR PHARMACEUTICS, vol. 11, p. 3760-3765, ISSN: 1543-8384, doi: 10.1021/mp500374f
Delli Castelli, Daniela, Ferrauto, Giuseppe, Cutrin, Juan Carlos, Terreno, Enzo, AIME, Silvio (2014). In Vivo Maps of Extracellular pH in Murine Melanoma by CEST–MRI. MAGNETIC RESONANCE IN MEDICINE, vol. 71, p. 326-332, ISSN: 0740-3194, doi: 10.1002/ mrm.24664
