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

Arvin Eskandari, Janine N. Boodram, Paul Brian Cressey, Chunxin Lu, Peter M. Bruno, Michael T. Hemann, Kogularamanan Suntharalingam

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)17867-17873
Number of pages7
JournalDalton Transactions
Volume45
Issue number44
Early online date13 Oct 2016
DOIs
Publication statusPublished - 28 Nov 2016

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