Developing <em>bis</em>-dithiolene based gadolinium free complexes for future application in photothermal therapy and bioimaging.

Abstract

Melanoma, a type of skin cancer originating from melanocytes, is a significant risk factor due to its potential for rapid metastasis and high mortality rates. Late diagnostics and inadequate treatments increase the possibility of tumor spreading to nearby tissues and organs and therefore, the probability to develop more aggressive cancers in organs as liver, lungs, brain, among others, in advanced cancer stages. Taking in to account the incidence statistics of the Latin America and Caribbean populations, and the increasing risk factor over the years, it is necessary to address the problem by using efficient and selective treatment. Therefore, development of new theranostic agents containing Ni bis-dithiolene complexes will be explored due to their diverse structural and electronic properties and their efficiency as photothermal agents (PTA) for photothermal (PTT) treatment.<br /> <br /> PTT have been considered as a potential alternative therapy to treat different types of cancer. The use of PTA provides the assistance to PTT through their strong near-infrared (NIR) absorbance, that can convert the radiation into heat to induce cell cancer death. Metal bis-dithiolene complexes have been studied as a good PTA because of their high conversion efficiency percentages and low toxicity in human cells. Before any treatment, a powerful diagnostic tool such as Magnetic Resonance Imaging (MRI) technique will be necessary to provide simultaneously anatomical and physiological information at a good spatial resolution. The use of MRI contrast agents (CAs) is needed for the acquisition of images with higher definition in order to perform a comprehensive study of the area of interest. Since the MRI technique has been used to obtain detailed images of organs and tissues within the body, helping in the detection of different types of tumors will serve as a complement for a specific therapy.<br /> <br /> Taking in to account all the properties required in contrast agents and photothermal agents, In this work, a family dithiolene ligands name as: dmit(acac)₂, dmio(acac)₂, dmit(3,5-dimethylpyrazole)₂, dmit(3,4-dimethoxybenzyl)₂, dmio(3,4-dimethoxybenzyl)₂, dmit(methylbenzoate)₂, dmio(methylbenzoate)₂, dmit(methylbenzoic acid)₂ and dmio(methylbenzoic acid)₂ were synthesized and characterized under spectroscopic techniques and studied as a non-innocent ligand from an electrochemical point of view. These non-innocent ligands were transformed to increase the coordination site and allowed the development of two Ni bis-dithiolene complexes with absorption characteristics in the Near Infrared (NIR) region. As photothermal agent candidates, the two synthesized complexes possess photostability characteristics. PT conversion efficiency was determined to be active photo-absorber with the capacity to transform energy to heat. The synthesized Ni bis-dithiolene complexes were characterized by spectroscopical and spectrometric as X-ray Diffraction, FT-IR, NMR, UV-Vis-NIR and MS techniques. The developed PTA agents were tested against malignant melanoma (A375) cancer cell line where the cell viability was determined to be more efficient at 48 h of treatment. Furthermore, the synthetized Ni bis-dithiolene complexes were tested against human osteoblast (hFOB 1.19) cell line where negligible toxicity was obtained after 24 h of treatment. The interference in bioimaging properties was evaluated comparing MnCl₂ and GBCA with standard (NBu₄)₂[Ni(dmit)₂], and the synthetized NiL5 and NiL7 to assess the capability as theranostic agents.