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Glycoconjugated Metal Complexes as Cancer Diagnostic and Therapeutic Agents
Authors:Giulia Bononi  Dalila Iacopini  Gaspare Cicio  Dr Sebastiano Di Pietro  Prof Carlotta Granchi  Prof Valeria Di Bussolo  Prof Filippo Minutolo
Affiliation:1. Dipartimento di Farmacia, Università di Pisa, Via Bonanno Pisano 33, 56126 Pisa, Italy;2. Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy;3. Dipartimento di Farmacia, Università di Pisa, Via Bonanno Pisano 33, 56126 Pisa, Italy

Current address: Menarini Ricerche S.p.A. –, Laboratori di Pisa, Via Livornese 897, 56122 Pisa, Italy

Abstract:The possibility of selectively delivering metal complexes to a defined cohort of cells on the basis of their metabolic features is a highly challenging goal, which may be extremely useful for a series of purposes, including diagnosis and therapy of pathological states, such as cancer. Tumor cells display augmented requests for carbohydrates and, in particular, for glucose in order to sustain their high proliferation rate, which causes an increased glycolytic process (Warburg effect). Since several metal complexes display diagnostic and/or therapeutic properties, their conjugation to carbohydrate portions often induce their preferential accumulation in cancer cells, similarly to what is observed with fluorodeoxyglucose (FDG). In this review we have considered the latest developments of glycoconjugates containing metal complexes in their structures. These compounds are classified as diagnostic or therapeutic agents and are further systematically discussed on the basis of the metal atom they contain. Several diagnostic techniques are possible with these probes, since, depending on the metal species included in their structures, they may be employed in nuclear medicine (PET, SPECT), magnetic resonance imaging, luminescence and phosphorescence. At the same time, the lack of selective cytotoxicity displayed by several metal-based chemotherapeutic agents, may also be solved by the conjugation of these agents to carbohydrate portions. Overall, data so far available reveal the great potential of this chemical class in the early detection and in the cure of severe neoplastic diseases, which still needs to be fully explored in the clinic.
Keywords:glycoconjugated complexes  cancer imaging  cancer therapy  Warburg effect  glycolytic metabolism
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