Glycoconjugated Metal Complexes as Cancer Diagnostic and Therapeutic Agents

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.

Reactive Oxygen Species Production Is Responsible for Antineoplastic Activity of Osmium, Ruthenium, Iridium and Rhodium Half-Sandwich Type Complexes with Bidentate Glycosyl Heterocyclic Ligands in Various Cancer Cell Models

“…Some of the complexes developed using other platinum-group metals apparently have advantageous properties compared to Pt-based drugs, e.g., better delivery properties [ 1 ], improved cellular entry under hypoxia [ 21 , 22 ], and a better toxicity profile [ 23 , 24 , 25 , 26 ]. These complexes can easily be directed to their biological targets by coupling to bait molecules, such as biotin, transferrin, hormones, or carbohydrates [ 1 , 27 , 28 , 29 ].…”

Ruthenium Half-Sandwich Type Complexes with Bidentate Monosaccharide Ligands Show Antineoplastic Activity in Ovarian Cancer Cell Models through Reactive Oxygen Species Production

“…Among the Ru(III)- and Ru(II)-based complexes, a great number of derivatives have been tested as anticancer metallodrugs, and two of them, the imidazolium salt of tetrachlorido(dimethylsulfoxide)(imidazole)ruthenium(III) ( Figure 1 , IV ) and sodium tetrachloridobis(indazole)ruthenium(III) ( V ), reached clinical trials [ 6 , 13 , 14 , 15 , 16 ]. The half-sandwich type Ru(II)-arene organometallics [ 17 ], due to a high structural variability, represent one of the most widely investigated compound classes in the development of new candidates of multitargeted metallodrugs [ 6 , 18 ]. The presence of an η 6 -arene or η 5 -arenyl residue in the coordination sphere contributes to the stabilization of the +2 oxidation state of the metal ion and to the maintenance of the hydrophilic/lipophilic balance of the whole molecule.…”

Square-Planar vs. Trigonal Bipyramidal Geometry in Pt(II) Complexes Containing Triazole-Based Glucose Ligands as Potential Anticancer Agents

“…One of the most successful strategies is the introduction of bio-active molecules in the coordination environment of the metal, capable of increasing its versatility and selectivity [17,18]. Among these, sugars are an excellent example due to their biocompatibility, the possibility of modulating their chemico-physical properties, and the ability of selective recognition by cancer cells, known as the Warburg effect [19][20][21][22][23][24][25][26][27][28]. In this context, over the last few years, our research group has proposed new organometallic glycoconjugate platinum complexes as innovative anticancer agents [29][30][31][32][33].…”