A series of 73 ligands and 73 of their Cu+2 and Cu+1 copper complexes with different geometries, oxidation states of the metal, and redox activities were synthesized and characterized. The aim of the study was to establish the structure–activity relationship within a series of analogues with different substituents at the N(3) position, which govern the redox potentials of the Cu+2/Cu+1 redox couples, ROS generation ability, and intracellular accumulation. Possible cytotoxicity mechanisms, such as DNA damage, DNA intercalation, telomerase inhibition, and apoptosis induction, have been investigated. ROS formation in MCF-7 cells and three-dimensional (3D) spheroids was proven using the Pt-nanoelectrode. Drug accumulation and ROS formation at 40–60 μm spheroid depths were found to be the key factors for the drug efficacy in the 3D tumor model, governed by the Cu+2/Cu+1 redox potential. A nontoxic in vivo single-dose evaluation for two binuclear mixed-valence Cu+1/Cu+2 redox-active coordination compounds, 72k and 61k, was conducted.
L-lysine α-oxidase (LO), one of L-amino acid oxidases, deaminates L-lysine with the yield of H2O2, ammonia, and α-keto-ε-aminocaproate. Multiple in vitro and in vivo studies have reported cytotoxic, antitumor, antimetastatic, and antitumor activity of LO. Unlike asparaginase, LO has a dual mechanism of action: depletion of L-lysine and formation of H2O2, both targeting tumor growth. Prominent results were obtained on murine and human tumor models, including human colon cancer xenografts HCT 116, LS174T, and T47D with maximum T/C 12, 37, and 36%, respectively. The data obtained from human cancer xenografts in immunodeficient mice confirm the potential of LO as an agent for colon cancer treatment. In this review, we discuss recently discovered molecular mechanisms of biological action and the potential of LO as anticancer enzyme.
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Magnetic tissue engineering is one of the rapidly emerging and promising directions of tissue engineering and biofabrication where the magnetic field is employed as temporal removal support or scaffold. Iron oxide nanoparticles are used to label living cells and provide the desired magnetic properties. Recently, polymer microcapsules loaded with iron oxide nanoparticles have been proposed as a novel approach to designing magnetic materials with high local concentrations. These microcapsules can be readily internalized and retained intracellularly for a long time in various types of cells. The low cytotoxicity of these microcapsules was previously shown in 2D cell culture. This paper has demonstrated that cells containing these nontoxic nanomaterials can form viable 3D tissue spheroids for the first time. The spheroids retained labeled fluorescent microcapsules with magnetic nanoparticles without a detectable cytotoxic effect. The high concentration of packed nanoparticles inside the microcapsules enables the evident magnetic properties of the labeled spheroids to be maintained. Finally, magnetic spheroids can be effectively used for magnetic patterning and biofabrication of tissue-engineering constructs.
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