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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. | LitMetric

AI Article Synopsis

  • * Two complexes, 2a and 3c, are found to be more effective at killing CSC-enriched cells than salinomycin, with complex 3c being the most potent due to its generation of reactive oxygen species and inhibition of COX-2 activity.
  • * Additionally, encapsulating complex 3c in biodegradable nanoparticles improves its uptake by breast CSCs while reducing overall toxicity, marking a significant advancement in targeted cancer treatment strategies.

Article 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 NP) enhances breast CSC uptake and reduces overall toxicity. The nanoparticle formulation, 3c NP 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.

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Source
http://dx.doi.org/10.1039/c6dt03811eDOI Listing

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