Analytical methodologies for metallomics studies of antitumor Pt-containing drugs

Abstract

Pt-containing drugs are nowadays essential components in cancer chemotherapy. However, drug resistance and side effects limit the efficiency of the treatments. In order to improve the response to Pt-based drugs, different administration strategies or new Pt-compounds have been developed with little success. The reason for this failure could be that the mechanism of action of these drugs is not completely understood. In this way, metallomics studies may contribute to clarify the interactions of Pt-containing drugs within the organism. This review is mainly focused on the role of Analytical Chemistry on the study of the interactions between Pt-based drugs and biomolecules. A summary of the analytical techniques and the most common sample treatment procedures currently used in metallomics studies of these drugs is presented. Both are of paramount importance to study these complex samples preserving the drug-biomolecule interaction. Separation and detection techniques must be carefully selected in order to achieve the intended goals. The use of multidimensional hyphenated techniques is usually necessary for a better understanding of the Pt-based drugs interactions in the organism. An overview of Pt-drugs biological interactions is presented, considering the different sample matrices and the drugs course through the organism. Samples analysed in the included studies are blood, urine, cell cytosol, DNA as well as the drugs themselves and their derivatives. However, most of these works are based on in vitro experiments or incubations of standards, leading in some cases to contradictory results depending on the experimental conditions used. Though in vivo experiments represent a great challenge due to the high complexity and the low concentrations of the Pt-adducts in real samples, these studies must be undertaken to get a deeper understanding of the real interactions concerning Pt-containing drugs.

Synthesis of novel macrocyclic Schiff's‐base and its complexes having N2O2 group of donor atoms. Characterization and anticancer screening are studied

“…[7,8] Hydrazones are characterized by the presence of azomethine group (─CH═N─); they are good polydentate chelating agents that can form a variety of complexes with various transition metals and inner transition metals. [9][10][11][12][13][14][15][16][17] Metal complexes containing improved organic ligands are widely used in cancer chemotherapy. The great success in the clinical treatment of human malignancies has stimulated research in the area of inorganic antitumor agents, the application of which can be hampered by severe toxicity and development of resistance during therapy.…”

Quantification of Noble Metals in Biological and Environmental Samples

“…The bioaccumulation coefficient of cisplatin in cancer cells was reported to be 1.8-3.8. Separation techniques, in particular ion chromatography and CE, coupled with element-specific and molecular detectors enable investigation of various platinum species occurring under physiological conditions, which is fundamental for explanation of the metabolism and therapeutic properties of these drugs [42,116,[144][145][146][147][148][149][150][151][152]. The monohydrated complex of cisplatin, a product of hydrolysis occurring under low chloride concentrations in cancer cells, is considered the most reactive with DNA.…”

Biospeciation of tungsten in the serum of diabetic and healthy rats treated with the antidiabetic agent sodium tungstate

“…In general, the complexity of the clinical samples makes it necessary to perform prior fractionation/separation steps for the isolation of metal-biomolecule complexes [12]. Recent years have witnessed the introduction of complementary analytical techniques, like tandem HPLC-ICP-MS, for the separation of the metal-containing species and on-line high sensitive detection of the metal, and structural Mass Spectrometry (MS) techniques, such as MALDI-TOF and Electrospray Ionization (ESI)-MS [13,14].…”