Intracellular Fenton reaction based on mitochondria-targeted copper(<scp>ii</scp>)–peptide complex for induced apoptosis

Li, Xia; Hao, Sijia; Han, Ailing; Yang, Yayu; Fang, Guozhen; Liu, Jifeng; Wang, Shuo

doi:10.1039/c9tb00569b

Cited by 52 publications

(37 citation statements)

References 55 publications

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“…In the presence of oxygen, Cu +1 complexes are capable of generating a superoxide anion that can induce ROS formation in a Fenton-like reaction (Cu +1 L + O 2 → O 2 −. + Cu +2 L) [ 30 ]. We demonstrated intracellular ROS formation within a few hours of exposure to CuO NPs and NAC.…”

Section: Discussionmentioning

confidence: 99%

Copper-Containing Nanoparticles and Organic Complexes: Metal Reduction Triggers Rapid Cell Death via Oxidative Burst

Tsymbal

Moiseeva

Agadzhanian

et al. 2021

IJMS

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Copper-containing agents are promising antitumor pharmaceuticals due to the ability of the metal ion to react with biomolecules. In the current study, we demonstrate that inorganic Cu2+ in the form of oxide nanoparticles (NPs) or salts, as well as Cu ions in the context of organic complexes (oxidation states +1, +1.5 and +2), acquire significant cytotoxic potency (2–3 orders of magnitude determined by IC50 values) in combinations with N-acetylcysteine (NAC), cysteine, or ascorbate. In contrast, other divalent cations (Zn, Fe, Mo, and Co) evoked no cytotoxicity with these combinations. CuO NPs (0.1–1 µg/mL) together with 1 mM NAC triggered the formation of reactive oxygen species (ROS) within 2–6 h concomitantly with perturbation of the plasma membrane and caspase-independent cell death. Furthermore, NAC potently sensitized HCT116 colon carcinoma cells to Cu–organic complexes in which the metal ion coordinated with 5-(2-pyridylmethylene)-2-methylthio-imidazol-4-one or was present in the coordination sphere of the porphyrin macrocycle. The sensitization effect was detectable in a panel of mammalian tumor cell lines including the sublines with the determinants of chemotherapeutic drug resistance. The components of the combination were non-toxic if added separately. Electrochemical studies revealed that Cu cations underwent a stepwise reduction in the presence of NAC or ascorbate. This mechanism explains differential efficacy of individual Cu–organic compounds in cell sensitization depending on the availability of Cu ions for reduction. In the presence of oxygen, Cu+1 complexes can generate a superoxide anion in a Fenton-like reaction Cu+1L + O2 → O2−.+ Cu+2L, where L is the organic ligand. Studies on artificial lipid membranes showed that NAC interacted with negatively charged phospholipids, an effect that can facilitate the penetration of CuO NPs across the membranes. Thus, electrochemical modification of Cu ions and subsequent ROS generation, as well as direct interaction with membranes, represent the mechanisms of irreversible membrane damage and cell death in response to metal reduction in inorganic and organic Cu-containing compounds.

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Section: Discussionmentioning

confidence: 99%

Copper-Containing Nanoparticles and Organic Complexes: Metal Reduction Triggers Rapid Cell Death via Oxidative Burst

Tsymbal

Moiseeva

Agadzhanian

et al. 2021

IJMS

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“…In addition, the optimal pH value for iron-based Fenton reaction is usually pH 2-5, and the reaction rate is low in the neutral intracellular environment of tumor cells (pH7.4) ( Bao et al, 2021 ). The Fenton reaction rate of Cu(I) (1 × 10 4 M −1 s −1 ) is much higher than that of Fe (II) (76 M −1 s −1 ) ( Hu et al, 2019 ; Li et al, 2019 ; Lin et al, 2019 ). Meanwhile, the pH range required for the reaction of Cu(I) is wider than that of Fe(II), which can be carried out in weakly acidic and neutral media ( Ma et al, 2019 ).…”

Section: Ht Enhanced M-cdt Nanodrugsmentioning

confidence: 89%

Mitochondria-Targeting Chemodynamic Therapy Nanodrugs for Cancer Treatment

Chen

Wang

et al. 2022

Front. Pharmacol.

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Mitochondria, as one of the most critical subcellular organelles of cancer cells, are very vulnerable and often on the verge of oxidative stress. The classic chemodynamic therapy (CDT) directly employs endogenous chemical energy to trigger reactive oxygen species (ROS) burst and destroy tumor cells. However, the effectiveness of CDT is restricted by the limited diffusion distance and short half-life of ROS. From this perspective, the treatment method (mitochondria-targeting chemodynamic therapy nanodrugs, M-CDT nanodrugs) that can generate high levels of ROS at the mitochondrial site is extremely efficient and promising for cancer treatment. Currently, many emerging M-CDT nanodrugs have been demonstrated excellent spatial specificity and anti-cancer efficacy. In this minireview, we review various proof-of-concept researches based on different M-CDT nanodrugs designs to overcome the limits of the efficacy of CDT, mainly divided into four strategies: supplying H2O2, non-H2O2 dependent CDT, eliminating GSH and enhancing by hyperthermia therapy (HT). These well-designed M-CDT nanodrugs greatly increase the efficacy of CDT. Finally, the progress and potential of M-CDT nanodrugs are discussed, as well as their limitations and opportunities.

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“…Both reactions produce highly reactive ● OH, which ultimately severely damages cells [ 84 , 85 , 86 , 87 ]. The Fenton reaction can be used to induce apoptosis in cancer cells, where ● OH is formed on a copper ion [ 88 , 89 ].…”

Section: Reactive Oxygen Speciesmentioning

confidence: 99%

Detection of Oxidative Stress Induced by Nanomaterials in Cells—The Roles of Reactive Oxygen Species and Glutathione

Čapek

Roušar

2021

Molecules

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The potential of nanomaterials use is huge, especially in fields such as medicine or industry. Due to widespread use of nanomaterials, their cytotoxicity and involvement in cellular pathways ought to be evaluated in detail. Nanomaterials can induce the production of a number of substances in cells, including reactive oxygen species (ROS), participating in physiological and pathological cellular processes. These highly reactive substances include: superoxide, singlet oxygen, hydroxyl radical, and hydrogen peroxide. For overall assessment, there are a number of fluorescent probes in particular that are very specific and selective for given ROS. In addition, due to the involvement of ROS in a number of cellular signaling pathways, understanding the principle of ROS production induced by nanomaterials is very important. For defense, the cells have a number of reparative and especially antioxidant mechanisms. One of the most potent antioxidants is a tripeptide glutathione. Thus, the glutathione depletion can be a characteristic manifestation of harmful effects caused by the prooxidative-acting of nanomaterials in cells. For these reasons, here we would like to provide a review on the current knowledge of ROS-mediated cellular nanotoxicity manifesting as glutathione depletion, including an overview of approaches for the detection of ROS levels in cells.

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Intracellular Fenton reaction based on mitochondria-targeted copper(ii)–peptide complex for induced apoptosis

Abstract: Intracellular Fenton reaction-based mitochondria-targeted copper(ii)–peptide complex and Asc is developed for cancer cell treatment.

Cited by 52 publications

References 55 publications

Copper-Containing Nanoparticles and Organic Complexes: Metal Reduction Triggers Rapid Cell Death via Oxidative Burst

Copper-Containing Nanoparticles and Organic Complexes: Metal Reduction Triggers Rapid Cell Death via Oxidative Burst

Mitochondria-Targeting Chemodynamic Therapy Nanodrugs for Cancer Treatment

Detection of Oxidative Stress Induced by Nanomaterials in Cells—The Roles of Reactive Oxygen Species and Glutathione

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