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1.
Dalton Trans ; 52(44): 16451-16455, 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37873614

RESUMEN

An atomically precise Cu(I) macrocyclic complex Cu8I was developed for chemodynamic therapy (CDT) research. The {Cu8} macrocyclic skeleton gradually forms with the selective recognition of iodide ions, and the monitoring of intermediate fragments during Cu8I formation using time-dependent electrospray ionization mass spectrometry indicates the following possible formation process: [Cu1] → [Cu2] → [Cu3] → [Cu4] → [Cu5I] → [Cu6I] → [Cu7I] → [Cu8I] when recognized by iodide ions. Furthermore, the Cu(I)-mediated Fenton-like reaction in Cu8I catalyzes the production of toxic ˙OH from H2O2, which results in efficient tumor suppression.


Asunto(s)
Peróxido de Hidrógeno , Neoplasias , Humanos , Yoduros , Línea Celular Tumoral
2.
Dalton Trans ; 52(18): 6187-6193, 2023 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-37078601

RESUMEN

Increasing the reactive oxygen species (ROS) content at the tumor site is one of the effective strategies to promote intracellular oxidative stress and improve therapeutic efficiency. Herein, an atomically precise cinnamaldehyde-derived metal-organic Cu(I) complex (denoted as DC-OD-Cu) was rationally constructed. DC-OD-Cu could preferentially accumulate in the mitochondria of HeLa cells due to the mitochondria-targeting ability of triphenylphosphine, which was accompanied by the generation of large amounts of highly toxic hydroxyl radicals (˙OH) via Cu(I)-mediated Fenton-like reactions. Meanwhile, greater ROS generation jointly results in mitochondrial damage under white LED light irradiation. Furthermore, the in vitro and in vivo results suggested that DC-OD-Cu possesses favorable cytotoxicity and inhibits tumor growth. We believe that this research might provide a controllable strategy to construct multifunctional metal organic complexes for ROS-involved CDT.


Asunto(s)
Complejos de Coordinación , Humanos , Células HeLa , Especies Reactivas de Oxígeno , Complejos de Coordinación/farmacología , Luz , Mitocondrias , Línea Celular Tumoral , Peróxido de Hidrógeno
3.
Dalton Trans ; 51(47): 18054-18058, 2022 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-36373723

RESUMEN

A triphenylphosphine coordinated Cu(I) complex of Fc-OD-Cu was rationally designed for chemodynamic therapy (CDT) of cancer. The complex was capable of generating a highly toxic hydroxyl radical (˙OH) via a Fenton-like reaction induced by Cu(I) moieties and simultaneously mediated by ferrocene moieties. As a result, the CDT efficiency of Fc-OD-Cu is higher than that of Ba-OD-Cu (without ferrocene moieties) and Fc-OD (without Cu(I) moieties).


Asunto(s)
Compuestos Organofosforados , Metalocenos
4.
J Mater Chem B ; 10(26): 5086-5094, 2022 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-35730927

RESUMEN

Chemodynamic therapy (CDT), which uses agents to induce cell death by decomposing endogenous hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (˙OH), has been recognized as a promising approach to treat cancer. However, improving the efficiency of ˙OH production is considered one of the biggest challenges that limits the therapeutic efficacy of CDT. Herein, to controllably and efficiently induce oxidative damage through the production of ˙OH, we developed a new metal complex CDT agent with atomically precise structural characteristics as a deviation from traditional nanomaterial-CDT agents. The obtained CDT agent, a cinnamaldehyde derived copper(I) complex (denoted Cin-OD-Cu), was found to be continuously enriched in the mitochondria of A2780 ovarian carcinoma cells, which was accompanied by the generation of large amounts of ˙OH via Cu(I)-mediated Fenton-like reactions of H2O2, thereby stimulating oxidative stress in the mitochondria and eventually leading to cell death. Moreover, in vivo experiments showed that Cin-OD-Cu was capable of effectively inhibiting tumor growth with excellent biocompatibility. We believe this research enriches the limited selection of atomically precise metal complex CDT agents in particular for reactive oxygen species-mediated treatments aimed at inducing mitochondria oxidative damage; we anticipate that it will provide new insights into the development of novel, atomically precise agents for CDT.


Asunto(s)
Complejos de Coordinación , Neoplasias Ováricas , Acroleína/análogos & derivados , Línea Celular Tumoral , Cobre/química , Cobre/farmacología , Femenino , Humanos , Peróxido de Hidrógeno/metabolismo , Compuestos Organofosforados
5.
Dalton Trans ; 51(15): 5782-5787, 2022 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-35353878

RESUMEN

A triphenylphosphine-modified tetra-nuclear Cu(I) coordinated cluster was constructed for enhanced chemodynamic therapy (CDT) by increasing the number of metal centers. Once inside human bladder cancer (T24) cells, a larger amount of copper accumulated compared with the mono-nuclear Cu(I) complex; the additional copper could generate more •OH and then induce more obvious apoptosis via a Fenton-like reaction, thus further increasing the tumor inhibition effect and ultimately improving the CDT efficiency.


Asunto(s)
Cobre , Neoplasias , Línea Celular Tumoral , Humanos , Peróxido de Hidrógeno , Compuestos Organofosforados
7.
RSC Adv ; 10(11): 6297-6305, 2020 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-35496028

RESUMEN

Based on 1,2-dimethoxyphenyl (veratrole, open) and 1,2-methylenedioxyphenyl (pepper ring, close)-derived pyridine-triazole analogues, two groups of copper(ii) complexes, namely, Group I(C1-C3) and Group II(C4-C6) were synthesized and fully characterized. All ligands and complexes were tested in vitro by MTT assays on seven tumour cell lines (T24, Hep-G2, Sk-Ov-3, MGC-803, HeLa, A549 and NCI-H460) and one normal liver cell line (HL-7702). Surprisingly, the pepper-ring-derived complexes (C4-C6) showed significantly enhanced cytotoxicity compared with the 1,2-bimethoxyphenyl ring-derived complexes (C1-C3) and the standard anticancer drug cisplatin. Cellular uptake assays indicated that the Cu accumulation was consistent with cytotoxicity. In addition, flow cytometry and western blot analysis showed that the apoptosis of the leading complex C4 may be induced by the Bcl-2 family-mediated proteins through the mitochondrial dysfunction pathway. Furthermore, UV-vis and fluorescence spectroscopy assays revealed that C4 has stronger insertion-binding interactions with CT-DNA than C1 and the fluorescence of C1 and C4 with BSA is mainly quenched by static quenching.

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