The breast cancer stem cell potency of copper(II) complexes bearing nonsteroidal anti-inflammatory drugs and their encapsulation using polymeric nanoparticles
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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DOI：
10.1039/c6dt03811e
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发表时间：
2016-01-01
影响因子：
4
通讯作者：
Suntharalingam, Kogularamanan
中科院分区：
文献类型：
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作者：
Eskandari, Arvin;Boodram, Janine N.;Suntharalingam, Kogularamanan
我们报道了一系列含有非甾体抗炎药：萘普生、甲苯酚酸和吲哚美辛（2a-3c）的新型铜(II)-菲罗啉配合物的癌症干细胞（CSC）效力。其中两种复合物，2a和3c，杀死乳腺CSC富集的hmler - shead细胞（在单层和三维细胞培养中生长）的程度明显优于盐霉素（一种公认的CSC毒素）。作为该系列中最有效的复合物，3c通过产生细胞内活性氧（ROS）和抑制环氧化酶-2 （COX-2）活性来诱导其细胞毒性作用。使用可生物降解的甲氧基聚（乙二醇）-b-聚（D， l -乳酸-羟基乙酸）酸（PEG-PLGA）共聚物在适当的饲料（5%,3c NP5）中包封3c，可提高乳腺CSC的吸收并降低总体毒性。纳米粒子制剂3c NP5选择性地杀死乳腺癌细胞上的乳腺CSCs，并引起细胞对有效载荷3c的类似反应。据我们所知，这是第一个证明聚合纳米颗粒可以有效地将csc强效金属配合物输送到csc中的研究。
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.