Cu-related agents for cancer therapies

Wang, Chunhui; Yang, Xinda; Dong, Chunyan; Chai, Keke; Ruan, Juan; Shi, Shuo

doi:10.1016/j.ccr.2023.215156

Cited by 23 publications

(9 citation statements)

References 323 publications

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“…48 Among them, Cu-MOFs have garnered significant attention as a prospective nanomedicine platform for drug delivery and tumor treatment due to their high porosity, large surface area, excellent loading capacity, and biodegradability. 19 Cu-MOFs are a class of MOFs in which Cu + /Cu 2+ and organic ligands are connected by coordination bonds. Generally speaking, Cu-MOFs are prepared primarily by reaction between soluble copper salts with organic components in a homogeneous solution.…”

Section: Cu 2 Omentioning

confidence: 99%

Biocompatible Copper-Based Nanocomposites for Combined Cancer Therapy

Song,

Tan,

Zhou

et al. 2024

ACS Biomater. Sci. Eng.

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Copper (Cu) and Cu-based nanomaterials have received tremendous attention in recent years because of their unique physicochemical properties and good biocompatibility in the treatment of various diseases, especially cancer. To date, researchers have designed and fabricated a variety of integrated Cu-based nanocomplexes with distinctive nanostructures and applied them in cancer therapy, mainly including chemotherapy, radiotherapy (RT), photothermal therapy (PTT), chemodynamic therapy (CDT), photodynamic therapy (PDT), cuproptosis-mediated therapy, etc. Due to the limited effect of a single treatment method, the development of composite diagnostic nanosystems that integrate chemotherapy, PTT, CDT, PDT, and other treatments is of great significance and offers great potential for the development of the next generation of anticancer nanomedicines. In view of the rapid development of Cu-based nanocomplexes in the field of cancer therapy, this review focuses on the current state of research on Cu-based nanomaterials, followed by a discussion of Cu-based nanocomplexes for combined cancer therapy. Moreover, the current challenges and future prospects of Cu-based nanocomplexes in clinical translation are proposed to provide some insights into the design of integrated Cu-based nanotherapeutic platforms.

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Section: Cu 2 Omentioning

confidence: 99%

Biocompatible Copper-Based Nanocomposites for Combined Cancer Therapy

Song,

Tan,

Zhou

et al. 2024

ACS Biomater. Sci. Eng.

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“…When considering the antiproliferative potential of copper(II) complexes, special attention is given to Cu(II)–terpyridine systems. − The chelating ability of 2,2′:6′,2″-terpyridine (terpy) and its derivatives (R-terpy) enhances complex stability, and their molecular structures facilitate noncovalent interactions with DNA through the major groove, − π-stacking between the plane of the aromatic rings and DNA base pairs, − and electrostatic binding. − Moreover, many Cu(II)–terpyridine systems can generate reactive oxygen species (ROS), giving rise to damage in the cytoplasm, mitochondria, and DNA. ,,,− Importantly, a broad range of possible structural modifications for 2,2′:6′,2″-terpyridine provide opportunities to enhance the anticancer profile and reduce side effects of Cu-based anticancer agents. Substituents introduced into the terpy framework have been shown to control the electronic and structural features of the resulting Cu(II) complexes, and thus their cytotoxicity behavior. ,,,,,,,− Exemplarily, the five-coordinated Cu(II) complex [CuCl 2 (R-terpy)] with 1-methyl-1 H -pyrrol-2-yl-2,2′:6′,2″-terpyridine exhibiting a rare trigonal-bipyramidal geometry induced by the bulky 1-methyl-1 H -pyrrole substituent, demonstrated no cytotoxic activity in tumor HCT116, A2780, A549, and MCF7 cell lines .…”

Section: Introductionmentioning

confidence: 99%

Copper(II) Complexes with 2,2′:6′,2″-Terpyridine Derivatives Displaying Dimeric Dichloro−μ–Bridged Crystal Structure: Biological Activities from 2D and 3D Tumor Spheroids to In Vivo Models

Choroba,

Machura,

Erfurt

et al. 2024

J. Med. Chem.

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Eight 2,2′:6′,2″-terpyridines, substituted at the 4′position with aromatic groups featuring variations in π-conjugation, ring size, heteroatoms, and methoxy groups, were employed to enhance the antiproliferative potential of [Cu 2 Cl 2 (R-terpy) 2 ]-(PF 6 ) 2 . Assessing the cytotoxicity in A2780 (ovarian carcinoma), HCT116 (colorectal carcinoma), and HCT116DoxR (colorectal carcinoma resistant to doxorubicin) and normal primary fibroblasts revealed that Cu(II) complexes with 4-quinolinyl, 4-methoxy-1naphthyl, 2-furanyl, and 2-pyridynyl substituents showed superior therapeutic potential in HCT116DoxR cells with significantly reduced cytotoxicity in normal fibroblasts (42−129× lower). Besides their cytotoxicity, the Cu(II) complexes are able to increase intracellular ROS and interfere with cell cycle progression, leading to cell death by apoptosis and autophagy. Importantly, they demonstrated antimetastatic and antiangiogenic properties without in vivo toxicity. In accordance with their nuclear accumulation, the Cu(II) complexes are able to cleave pDNA and interact with bovine serum albumin, which is a good indication of their ability for internalization and transport toward tumor cells.

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“…Various copper ionophores, such as disulfiram and elesclomol, have been developed for enhanced cuproptosis. 20,21 However, such small molecule drugs face the challenge of a lack of selectivity and difficulty in tumor retention. In contrast, the suitable size of nanocarriers allows Cu to preferentially accumulate in tumor tissue.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the development of advanced copper carriers is urgently needed. Various copper ionophores, such as disulfiram and elesclomol, have been developed for enhanced cuproptosis. , However, such small molecule drugs face the challenge of a lack of selectivity and difficulty in tumor retention. In contrast, the suitable size of nanocarriers allows Cu to preferentially accumulate in tumor tissue. , Hence, developing a multifunctional nanosystem that simultaneously triggers SDT and enables copper delivery is a rational strategy for inducing synergistic SDT/cuproptosis for effective cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Bioactive Layered Double Hydroxides for Synergistic Sonodynamic/Cuproptosis Anticancer Therapy with Elicitation of the Immune Response

Tang,

Wu,

Wang

et al. 2024

ACS Nano

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Sonodynamic therapy (SDT) has promising application prospects in tumor therapy. However, SDT does not eradicate metastatic tumors. Herein, Cu-substituted ZnAl ternary layered double hydroxide nanosheets (ZCA NSs) were developed as both sonosensitizers and copper nanocarriers for synergistic SDT/cuproptosis cancer therapy. An optimized electronic structure more conducive to the sonodynamic process was obtained from ZCA NSs via the Jahn−Teller effect induced by the introduction of Cu 2+ , and the synthesized ZCA NSs regulated the intricate tumor microenvironment (TME) by depleting endogenous glutathione (GSH) to amplify oxidative stress for further enhanced SDT performance. Furthermore, cuproptosis was evoked by intracellular overload of Cu 2+ and amplified by SDT, leading to irreversible proteotoxicity. In vitro results showed that such synergetic SDT/cuproptosis triggered immunogenic cell death (ICD) and promoted the maturation of dendritic cells (DCs). Furthermore, the as-synthesized ZCA NS-mediated SDT/ cuproptosis thoroughly eradicated the in vivo solid tumors and simultaneously elicited antitumor immunity to suppress lung and liver metastasis. Overall, this work established a nanoplatform for synergistic SDT/cuproptosis with a satisfactory antitumor immunity.

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Cu-related agents for cancer therapies

Cited by 23 publications

References 323 publications

Biocompatible Copper-Based Nanocomposites for Combined Cancer Therapy

Biocompatible Copper-Based Nanocomposites for Combined Cancer Therapy

Copper(II) Complexes with 2,2′:6′,2″-Terpyridine Derivatives Displaying Dimeric Dichloro−μ–Bridged Crystal Structure: Biological Activities from 2D and 3D Tumor Spheroids to In Vivo Models

Bioactive Layered Double Hydroxides for Synergistic Sonodynamic/Cuproptosis Anticancer Therapy with Elicitation of the Immune Response

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