Schlüsselwörter
(Englisch)
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Lanthanide; luminescene; bioprobe; cancer cell; biomarker; time-resolved luminescence microscopy
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Forschungsprogramme
(Englisch)
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COST-Action D38 - Meta-based Systems for Molecular Imaging Applications
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Kurzbeschreibung
(Englisch)
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This research proposal focuses on the construction of functionalized luminescent lanthanide probes for targeting specific epitopes on cellular membranes, a subject of increasing attention in the context of medical diagnostics and cancer treatment. The chosen tags are bimetallic triple helical molecules obtained by self assembly in water from ditopic ligands and trivalent lanthanide ions. They have been chosen in view of a future extension of the project to dual (heterobimetallic) and chiral probes. We plan the design of ligands bearing various targeting groups such as peptides and antibodies, and the study of the selective recognition of these luminescent complexes by living cancer cells. Additionally, the analytical potential of the bimetallic helicates will be assessed.
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Weitere Hinweise und Angaben
(Englisch)
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Full name of research-institution/enterprise: EPF Lausanne Laboratoire de chimie supramoléculaire des lanthanides (LCSL) ISIC
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Partner und Internationale Organisationen
(Englisch)
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BE, CH, CY, CZ, DE, ES, FI, FR, GR, HU, IT, NL, PL, PT, TR, UK
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Abstract
(Englisch)
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The project developed along three lines. Firstly, lanthanide luminescent binuclear helicates have been synthesized and tested with respect to their ability to serve as luminescent bioprobes. The design of the bioprobes took into consideration (i) the easiness of synthesis, the chelates self-assembling in water at room temperature, (ii) their robustness both with respect to thermodynamic stability and kinetic inertness, (iii) their potential chirality (not yet exploited) and (iv) their featuring two functional metal ions in one molecule. The ligand system chosen proved to be versatile in that it sensitizes the luminescence of several lanthanide ions, opening the way to multiplex analyses. The non-cytotoxic chelates permeate into live cancerous and non-cancerous cells by endocytosis and localize in the endoplasmatic reticulum., without much egress. They allow time-resolved detection, henceforth freeing the images from unwanted background signals. Secondly, bioconjugation of the helicates with avidin and/or specific monoclonal antibodies resulted in the selective targeting of human breast cancer cells through recognition of the 5D10 antigen expressed by these cells. Finally, a simple microfluidic device has been fabricated for either culturing cells faster than in regular culture media or for the analysis of tissue sections. A collaboration with the university hospital resulted in the establishment of an analysis method for two receptors expressed by breast cancer cells, the estrogen receptors and the human epidermal growth factor receptors. Simultaneous analysis of these two receptors is performed in time-resolved mode in 5-6 fold less time (20 min) than in pathology laboratories and necessitates 5-10 times less (very expensive) reactants. The methods is now being tested on a statistically significant set of tissue sections and if transposition to day-to-day practice is successful, this will result in a huge decrease in the analysis cost (a good news for health insurances). In parallel, a real-time device is now being engineered, which features a much reduced analysis time (5 min) and which should be useable by surgeons and medical doctors.
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Datenbankreferenzen
(Englisch)
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Swiss Database: COST-DB of the State Secretariat for Education and Research Hallwylstrasse 4 CH-3003 Berne, Switzerland Tel. +41 31 322 74 82 Swiss Project-Number: C07.0116
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