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Issue 44, 2016
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The breast cancer stem cell potency of copper(II) complexes bearing nonsteroidal anti-inflammatory drugs and their encapsulation using polymeric nanoparticles

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Abstract

We report the cancer stem cell (CSC) potency of a novel series of copper(II)-phenanthroline complexes bearing nonsteriodial anti-inflammatory drugs: naproxen, tolfenamic acid, and indomethacin (2a–3c). Two of the complexes, 2a and 3c, kill breast CSC-enriched HMLER-shEcad cells (grown in both monolayer and three-dimensional cell cultures) to a significantly better extent than salinomycin, a well-established CSC toxin. The most potent complex in the series, 3c induces its cytotoxic effect by generating intracellular reactive oxygen species (ROS) and inhibiting cyclooxgenase-2 (COX-2) activity. Encapsulation of 3c using biodegradable methoxy poly(ethylene glycol)-b-poly(D,L-lactic-co-glycolic) acid (PEG–PLGA) copolymers at the appropriate feed (5%, 3c NP5) enhances breast CSC uptake and reduces overall toxicity. The nanoparticle formulation, 3c NP5 selectively kills breast CSCs over bulk breast cancer cells, and evokes a similar cellular response to the payload, 3c. To the best of our knowledge, this is the first study to demonstrate that polymeric nanoparticles can be used to effectively deliver CSC-potent metal complexes into CSCs.

Graphical abstract: The breast cancer stem cell potency of copper(ii) complexes bearing nonsteroidal anti-inflammatory drugs and their encapsulation using polymeric nanoparticles

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Publication details

The article was received on 01 Oct 2016, accepted on 13 Oct 2016 and first published on 13 Oct 2016


Article type: Paper
DOI: 10.1039/C6DT03811E
Citation: Dalton Trans., 2016,45, 17867-17873
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    The breast cancer stem cell potency of copper(II) complexes bearing nonsteroidal anti-inflammatory drugs and their encapsulation using polymeric nanoparticles

    A. Eskandari, J. N. Boodram, P. B. Cressey, C. Lu, P. M. Bruno, M. T. Hemann and K. Suntharalingam, Dalton Trans., 2016, 45, 17867
    DOI: 10.1039/C6DT03811E

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