Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance
Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance
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DOI：
10.1073/pnas.2232479100
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发表时间：
2003-11-11
影响因子：
11.1
通讯作者：
West, JL
中科院分区：
文献类型：
--
作者：
Hirsch, LR;Stafford, RJ;West, JL
金属纳米壳是一类具有可调谐光学共振的纳米粒子。在本文中，描述了这项技术在癌症热消融治疗中的一种应用。通过将纳米壳调谐到强烈吸收近红外光（在此波段光在组织中的传输最佳），组织深处的纳米壳分布可通过使用适度低剂量的体外施加近红外（NIR）光来传递治疗剂量的热量。体外培养并与纳米壳一起孵育的人乳腺癌细胞在暴露于近红外光（820纳米，35瓦/平方厘米）时，经荧光活性染色测定，发现发生了光热诱导的病变。在相同的近红外光照时间和条件下，没有纳米壳的细胞未显示出活性损失。同样，在磁共振引导下的体内研究表明，在使用金属纳米壳治疗的实体瘤中，暴露于低剂量的近红外光（820纳米，4瓦/平方厘米）时，在4 - 6分钟内达到了能够引起不可逆组织损伤的平均最高温度（ΔT = 37.4 ± 6.6℃）。未用纳米壳处理的对照组在暴露于近红外光时平均温度明显较低（ΔT < 10℃）。这些发现与组织学结果有良好的相关性。加热到热损伤阈值以上的组织显示出凝固、细胞皱缩和核染色缺失，这些都是不可逆热损伤的指标。对照组织未出现损伤。
Metal nanoshells are a class of nanoparticles with tunable optical resonances. In this article, an application of this technology to thermal ablative therapy for cancer is described. By tuning the nanoshells to strongly absorb light in the near infrared, where optical transmission through tissue is optimal, a distribution of nanoshells at depth in tissue can be used to deliver a therapeutic dose of heat by using moderately low exposures of extracorporeally applied near-infrared (NIR) light. Human breast carcinoma cells incubated with nanoshells in vitro were found to have undergone photothermally induced morbidity on exposure to NIR light (820 nm, 35 W/cm(2)), as determined by using a fluorescent viability stain. Cells without nanoshells displayed no loss in viability after the same periods and conditions of NIR illumination. Likewise, in vivo studies under magnetic resonance guidance revealed that exposure to low doses of NIR light (820 nm, 4 W/cm(2)) in solid tumors treated with metal nanoshells reached average maximum temperatures capable of inducing irreversible tissue damage (DeltaT = 37.4 +/- 6.6degreesC) within 4-6 min. Controls treated without nanoshells demonstrated significantly lower average temperatures on exposure to NIR light (DeltaT < 10degreesC). These findings demonstrated good correlation with histological findings. Tissues heated above the thermal damage threshold displayed coagulation, cell shrinkage, and loss of nuclear staining, which are indicators of irreversible thermal damage. Control tissues appeared undamaged.