The potential use of the enhanced nonlinear properties of gold nanospheres in photothermal cancer therapy
The potential use of the enhanced nonlinear properties of gold nanospheres in photothermal cancer therapy
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DOI：
10.1002/lsm.20577
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发表时间：
2007-10-01
影响因子：
2.4
通讯作者：
El-Sayed, Mostafa A.
中科院分区：
文献类型：
--
作者：
Huang, Xiaohua;Qian, Wei;El-Sayed, Mostafa A.
背景和目的：激光光热疗法(PTT)目前正在使用短激光脉冲进行治疗。利用等离子体纳米粒子作为造影剂，可以利用纳米粒子的光学性质降低激光能量，通过粒子表面的分子探针提高肿瘤的选择性。在这项研究中，我们旨在利用聚集的球形金纳米粒子与抗表皮生长因子受体(抗EGFR)抗体在短时间近红外激光脉冲作用下的非线性光学性质来选择性和高效地进行PTT。研究设计/材料和方法：合成球形金纳米粒子，并将其与抗EGFR抗体偶联，以特异性靶向HSC口腔癌细胞。用显微吸收光谱和暗场光散射成像对纳米颗粒进行了表征。用800 nm、脉冲宽度为100飞秒、重复频率为1 kHz的飞秒钛宝石激光对对照癌细胞和纳米颗粒处理的癌细胞进行光热破坏。结果：纳米粒子处理后对细胞的激光功率阈值比正常PTT(即不含纳米粒子的PTT)的激光功率阈值低20倍。被破坏细胞的数量与激光功率呈二次曲线关系。死亡细胞的数量与专门针对癌细胞的金纳米颗粒的浓度呈非线性关系。结论：利用抗EGFR抗体偶联的球形金纳米粒子的等离子体增强的非线性光学过程，可以大大提高PTT的能量阈值和选择性。光热效率与脉冲近红外激光功率的二次关系表明存在二次谐波产生或双光子吸收过程。观察到的金纳米粒子浓度的非线性依赖关系表明，聚集的纳米球是导致观察到的细胞光热破坏增强的原因。
Background and Objective: Laser photothermal therapy (PTT) is practiced at the moment using short laser pulses. The use of plasmonic nanoparticles as contrast agents can decrease the laser energy by using the optical property of the nanoparticles and improve the tumor selectivity by the molecular probes on the particle surface. In this study, we aim at selective and efficient PTT by exploiting the nonlinear optical properties of aggregated spherical gold nanoparticles conjugated to anti-epidermal growth factor receptor (anti-EGFR) antibodies using short NIR laser pulses. Study Design/Materials and Methods: Spherical gold nanoparticles are synthesized and conjugated to anti-EGFR antibodies to specifically target HSC oral cancer cells. The nanoparticles are characterized by micro-absorption spectra and dark field light scattering imaging. Photothermal destructions of control and nanoparticle treated cancer cells are carried out with a ferntosecond Ti:Sapphire laser at 800 nm with a pulse duration of 100 femtoseconds and repetition rate of 1 kHz. Results: The laser power threshold for the photothermal destruction of cells after the nanoparticle treatment is found to be 20 times lower than that required to destroy the cells in the normal PTT, that is, without nanoparticles. The number of destroyed cells is quadratically dependent on the laser power. The number of dead cells shows a nonlinear dependence on the concentration of gold nanoparticles that are specifically targeted to cancer cells. Conclusions: The energy threshold and selectivity of PTT can greatly benefit from the use of the plasmonic enhanced nonlinear optical processes of spherical gold nanoparticles conjugated to anti-EGFR antibodies. The quadratic dependence of the photothermal efficiency on the pulsed NIR laser power indicates a second harmonic generation or a two photon absorption process. The observed nonlinear dependence on the gold nanoparticle concentration suggests that aggregated nanospheres are responsible for the observed enhanced photothermal destruction of the cells.