Chemical Engineering, Arizona State University, Tempe, Arizona 85287-6106, USA.
ACS Nano. 2010 May 25;4(5):2892-900. doi: 10.1021/nn901884d.
Plasmonic nanoparticles have shown promise in hyperthermic cancer therapy, both in vitro and in vivo. Previous reports have described hyperthermic ablation using targeted and nontargeted nanoparticles internalized by cancer cells, but most reports do not describe a theoretical analysis for determining optimal parameters. The focus of the current research was first to evaluate the spatiotemporal temperature distribution and cell death induced by extracellular hyperthermia in which gold nanorods (GNRs) were maintained in the dispersion outside human prostate cancer cells. The nanorod dispersion was irradiated with near-infrared (NIR) laser, and the spatiotemporal distribution of temperature was determined experimentally. This information was employed to develop and validate theoretical models of spatiotemporal temperature profiles for gold nanorod dispersions undergoing laser irradiation and the impact of the resulting heat generation on the viability of human prostate cancer cells. A cell injury/death model was then coupled to the heat transfer model to predict spatial and temporal variations in cell death and injury. The model predictions agreed well with experimental measurements of both temperature and cell death profiles. Finally, the model was extended to examine the impact of selective binding of gold nanorods to cancer cells compared to nonmalignant cells, coupled with a small change in cell injury activation energy. The impact of these relatively minor changes results in a dramatic change in the overall cell death rate. Taken together, extracellular hyperthermia using gold nanorods is a promising strategy, and tailoring the cellular binding efficacy of nanorods can result in varying therapeutic efficacies using this approach.
等离子体纳米粒子在体外和体内的高热癌症治疗中都显示出了前景。以前的报告描述了使用被癌细胞内化的靶向和非靶向纳米粒子进行高热消融，但大多数报告没有描述确定最佳参数的理论分析。目前研究的重点首先是评估金纳米棒（GNRs）在分散体中保持在人前列腺癌细胞外时，细胞外高温引起的时空温度分布和细胞死亡。纳米棒分散体用近红外（NIR）激光照射，实验测定温度的时空分布。该信息用于开发和验证金纳米棒分散体在激光照射下时空温度分布的理论模型以及由此产生的热产生对人前列腺癌细胞活力的影响。然后将细胞损伤/死亡模型与传热模型耦合，以预测细胞死亡和损伤的时空变化。模型预测与温度和细胞死亡曲线的实验测量吻合良好。最后，该模型扩展到研究与非恶性细胞相比，金纳米棒对癌细胞的选择性结合以及细胞损伤激活能的微小变化对细胞死亡率的影响。这些相对较小的变化的影响导致整体细胞死亡率发生显著变化。综上所述，使用金纳米棒的细胞外高温是一种很有前途的策略，通过调整纳米棒的细胞结合效率，可以使用这种方法产生不同的治疗效果。
