Tetranuclear copper(ii) complexes containing multiple diclofenac and Schiff base moieties, 1-4, are shown to kill bulk cancer cells and cancer stem cells (CSCs) with low micromolar potency. The most effective complex, 1, elicits its cytotoxic effect by elevating the intracellular reactive oxygen species (ROS) levels and inhibiting cyclooxygenase-2 (COX-2) expression.

The breast cancer stem cell (CSC) and bulk breast cancer cell potency of a series of metallopeptides containing dichloro(1,10-phenanthroline)copper(II) and various organelle-targeting peptide sequences is reported. The mitochondria-targeting metallopeptide 1 exploits the higher mitochondrial load in breast CSCs over the corresponding non-CSCs and the vulnerability of breast CSCs to mitochondrial damage to potently and selectively kill breast CSCs. Strikingly, 1 reduces the formation and size of mammospheres to a greater extent than salinomycin, an established CSC-potent agent. Mechanistic studies show that 1 enters CSC mitochondria, induces mitochondrial dysfunction, generates reactive oxygen species (ROS), activates JNK and p38 pathways, and prompts apoptosis. To the best of our knowledge, 1 is the first metallopeptide to selectivity kill breast CSCs in vitro.

Thermogalvanic cells can act like ‘liquid thermoelectrics’ to convert a thermal energy gradient to electrical energy. Such cells are typically combined electrically in-series in devices to boost the output voltage...

Cancer stem cells (CSCs) are heavily linked to fatal incidences of cancer relapse and metastasis. Conventional cancer therapies such as surgery, chemotherapy and radiation are largely futile against CSCs. Therefore, highly original approaches are needed to overcome CSCs and to provide durable, long-term clinical outcomes. Many academia- and pharmaceutical-led studies aimed at developing chemical or biological anti-CSC agents are ongoing; however, the application of inorganic compounds is rare. In this minireview, we discuss how the chemical diversity and versatility offered by metals has been harnessed to develop an unprecedented, emerging class of metallopharmaceuticals: CSC-active inorganics. A detailed account of their mechanism(s) of action is provided, and possible future directions for exploration are also put forward.

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