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Review
. 2022 Mar 4:9:841814.
doi: 10.3389/fmolb.2022.841814. eCollection 2022.

Selective Targeting of Cancer Cells by Copper Ionophores: An Overview

Valentina Oliveri  1
Affiliations
Review

Selective Targeting of Cancer Cells by Copper Ionophores: An Overview

Valentina Oliveri (VSports最新版本). Front Mol Biosci. .

"V体育2025版" Abstract

Conventional cancer therapies suffer from severe off-target effects because most of them target critical facets of cells that are generally shared by all rapidly proliferating cells. The development of new therapeutic agents should aim to increase selectivity and therefore reduce side effects. In addition, these agents should overcome cancer cell resistance and target cancer stem cells. Some copper ionophores have shown promise in this direction thanks to an intrinsic selectivity in preferentially inducing cuproptosis of cancer cells compared to normal cells VSports手机版. Here, Cu ionophores are discussed with a focus on selectivity towards cancer cells and on the mechanisms responsible for this selectivity. The proposed strategies, to further improve the targeting of cancer cells by copper ionophores, are also reported. .

Keywords: ROS; anticancer; chemotherapeutics; copper ionophores; cuproplasia; cuproptosis; prodrug. V体育安卓版.

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VSports注册入口 - Conflict of interest statement

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor and reviewers QD and XC declared their involvement as co-editors in the Research Topic, and confirm the absence of any other collaboration V体育ios版.

Figures

FIGURE 1
FIGURE 1
(A) Cu chelators inhibit cuproplasia (a Cu-dependent cellular proliferation), decreasing the intracellular Cu concentration; (B) Cu ionophores induce cuproptosis, increasing the intracellular (in particular in mitochondria) Cu levels and leading to cell death; (C) the intrinsic selectivity of Cu ionophores results from different factors: the increased Cu levels in cancer tissues, the enhanced levels of ROS species that make cancer cells more susceptible to a further increase of oxidative stress, the targeting of receptors overexpressed in cancer cells.
FIGURE 2
FIGURE 2
Schematic representation of a generic proionophore and a Nano Drug Delivery System that selectively deliver the ionophore to cancer cells, exploiting a targeting unit.
FIGURE 3
FIGURE 3
Chemical structure of PNap and the proposed mechanism for the release of Nap upon the action of H2O2 and a spontaneous 1,6 benzyl elimination. Then, Nap is alkylated by GSH and acts as a Cu ionophore. The arrows highlight the processes, which occur intracellularly (GSH depletion and Cu accumulation).
FIGURE 4
FIGURE 4
Chemical structure of PHQ, DQ, and GGTDTC and the proposed mechanism for the release of the active ionophores (3-HF and DTC).
Figure 5
Figure 5
Chemical structures of the proionophores (RPD and HPD) and the proposed mechanism for the release of DTC upon the action of PSA, a generic aminopeptidase, and a spontaneous 1,6 benzyl elimination.
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VSports注册入口 - References

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