Nanoshell-mediated photothermal therapy can enhance chemotherapy in inflammatory breast cancer cells.
Nanoshell-mediated photothermal therapy can enhance chemotherapy in inflammatory breast cancer cells.
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DOI：
10.2147/ijn.s93031
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发表时间：
2015
影响因子：
8
通讯作者：
Day ES
中科院分区：
文献类型：
--
作者：
Fay BL;Melamed JR;Day ES
纳米壳介导的光热疗法(PTT)目前正在作为一种独立的癌症治疗方法进行研究。PTT的细胞效应包括膜完整性的丧失，因此我们假设纳米壳介导的PTT可以通过改善肿瘤细胞中的药物积聚来增强化疗的细胞毒性。在这项工作中，我们使用阿霉素作为模型药物和SUM149炎性乳腺癌细胞作为模型癌症亚型来验证我们的假设。在最初的研究中，SUM149细胞暴露在纳米壳和近红外光下，然后用乙锭高二聚体-1染色，这是从质膜完整的细胞中排除的。结果证实，纳米壳介导的PTT能增加SUM149细胞的膜通透性。在补充实验中，用纳米壳、近红外光或两者的组合处理SUM149细胞以产生低剂量的PTT，并将其暴露在荧光罗丹明123中。通过流式细胞仪分析细胞内罗丹明123的荧光，证实PTT引起的膜通透性增加可以促进药物在细胞内的积累。用荧光显微镜评估阿霉素在细胞内的分布证实了这一点。在随后的实验中，将SUM149细胞暴露于亚治疗水平的阿霉素、低剂量PTT或两种治疗方法的组合，以确定PTT诱导的额外药物摄取是否足以增强细胞死亡。分析显示，与对照组相比，暴露于亚治疗水平阿霉素的细胞活力损失最小，暴露于低剂量PTT的细胞活力损失15%，暴露于联合治疗的细胞活力损失35%。这些数据表明，纳米壳介导的PTT是一种增强化疗效果的可行策略，并值得使用其他药物和癌症亚型进一步研究这一方法。
Nanoshell-mediated photothermal therapy (PTT) is currently being investigated as a standalone therapy for the treatment of cancer. The cellular effects of PTT include loss of membrane integrity, so we hypothesized that nanoshell-mediated PTT could potentiate the cytotoxicity of chemotherapy by improving drug accumulation in cancer cells. In this work, we validated our hypothesis using doxorubicin as a model drug and SUM149 inflammatory breast cancer cells as a model cancer subtype. In initial studies, SUM149 cells were exposed to nano-shells and near-infrared light and then stained with ethidium homodimer-1, which is excluded from cells with an intact plasma membrane. The results confirmed that nanoshell-mediated PTT could increase membrane permeability in SUM149 cells. In complementary experiments, SUM149 cells treated with nanoshells, near-infrared light, or a combination of the two to yield low-dose PTT were exposed to fluorescent rhodamine 123. Analyzing rhodamine 123 fluorescence in cells via flow cytometry confirmed that increased membrane permeability caused by PTT could enhance drug accumulation in cells. This was validated using fluorescence microscopy to assess intracellular distribution of doxorubicin. In succeeding experiments, SUM149 cells were exposed to subtherapeutic levels of doxorubicin, low-dose PTT, or a combination of the two treatments to determine whether the additional drug uptake induced by PTT is sufficient to enhance cell death. Analysis revealed minimal loss of viability relative to controls in cells exposed to subtherapeutic levels of doxorubicin, 15% loss of viability in cells exposed to low-dose PTT, and 35% loss of viability in cells exposed to combination therapy. These data indicate that nanoshell-mediated PTT is a viable strategy to potentiate the effects of chemotherapy and warrant further investigation of this approach using other drugs and cancer subtypes.