Synthetic beidellite clay as nanocarrier for delivery of antitumor oxindolimine-metal complexes

Autor(es)

Couto, Ricardo Alexandre Alves ; Miguel, Rodrigo Bernardi ; Vieira, Eduardo Guimaraes ; Brendle, Jocelyne ; Limousy, Lionel ; Constantino, Vera Regina Leopoldo ; Ferreira, Ana Maria Da Costa

• Tipo de documento: Artigo Científico
• Fonte: Journal of Inorganic Biochemistry; v. 240, p. 12-pg., 2022-12-28.

Resumo

Studies on the immobilization of oxindolimine-copper(II) or zinc(II) complexes [ML] in synthetic beidellite (BDL) clay were developed to obtain a suitable inorganic carrier capable of promoting the modified-release of metallopharmaceuticals. Previous investigations have shown that the studied metal complexes are promising antitumor agents, targeting DNA, mitochondria, and some proteins. They can bind to DNA, causing oxidative damage via formation of reactive oxygen species (ROS). In mitochondria they lead to a decrease in membrane potential, acting as decoupling agents, and therefore efficiently inducing apoptosis. Additionally, they inhibit human topoisomerase IB and cyclin dependent kinases, proteins involved in the cell cycle. BDL clays in the sodium form were synthesized under hydrothermal conditions and characterized by a set of physicochemical techniques while the BDL-[ML] hybrid materials were prepared by ion exchange method. The characterization of pristine clay and the obtained hybrids were performed by Infrared, Raman, electron paramagnetic resonance and energy dispersive X-ray spectroscopies, thermogravimetric analysis, scanning electron microscopy, X-ray powder diffraction, specific surface area, zeta potential and surface ionic charge measurements. The [ML] release assays under the same cell incubation conditions were performed monitoring metals by X-ray fluorescence. The BDL-[CuL] hybrid materials were stable and able to derail tumor HeLa cells, with corresponding IC50 values in the 0.11-0.41 mg mL-1 range. By contrast, the analogous hybrid samples of zinc(II) and the pristine BDL proved to be non-toxic facing the same cells. These results indicate a promising possibility of using synthetic beidellite as a carrier of such antitumor metal complexes. (AU)

• Processo FAPESP: 11/50318-1 - Desenvolvimento de compostos com interesse farmacológico ou medicinal e de sistemas para seu transporte, detecção e reconhecimento no meio biológico
• Beneficiário: Ana Maria da Costa Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/50317-9 - Biocompatible nanovectors based on hybrid lamellar materials and composites with polymers for drug release
• Beneficiário: Vera Regina Leopoldo Constantino
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/16735-8 - Imobilização de potenciais metalofármacos em matrizes inorgânicas ou orgânicas para liberação modificada
• Beneficiário: Eduardo Guimarães Vieira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado