School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, Virginia, USA.
Cancer Res. 2010 Dec 1;70(23):9855-64. doi: 10.1158/0008-5472.CAN-10-0250. Epub 2010 Nov 23.
This study demonstrates the capability of multiwalled carbon nanotubes (MWNTs) coupled with laser irradiation to enhance treatment of cancer cells through enhanced and more controlled thermal deposition, increased tumor injury, and diminished heat shock protein (HSP) expression. We also explored the potential promise of MWNTs as drug delivery agents by observing the degree of intracellular uptake of these nanoparticles. To determine the heat generation capability of MWNTs, the absorption spectra and temperature rise during heating were measured. Higher optical absorption was observed for MWNTs in water compared with water alone. For identical laser parameters, MWNT-containing samples produced a significantly greater temperature elevation compared to samples treated with laser alone. Human prostate cancer (PC3) and murine renal carcinoma (RENCA) cells were irradiated with a 1,064-nm laser with an irradiance of 15.3 W/cm(2) for 2 heating durations (1.5 and 5 minutes) alone or in combination with MWNT inclusion. Cytotoxicity and HSP expression following laser heating was used to determine the efficacy of laser treatment alone or in combination with MWNTs. No toxicity was observed for MWNTs alone. Inclusion of MWNTs dramatically decreased cell viability and HSP expression when combined with laser irradiation. MWNT cell internalization was measured using fluorescence and transmission electron microscopy following incubation of MWNTs with cells. With increasing incubation duration, a greater number of MWNTs were observed in cellular vacuoles and nuclei. These findings offer an initial proof of concept for the application of MWNTs in cancer therapy.
这项研究证明了多壁碳纳米管 (MWNTs) 与激光辐照相结合的能力,通过增强和更受控的热沉积、增加肿瘤损伤和减少热休克蛋白 (HSP) 表达来增强癌症细胞的治疗效果。我们还通过观察这些纳米粒子的细胞内摄取程度,探索了 MWNTs 作为药物递送剂的潜力。为了确定 MWNTs 的产热能力,测量了吸收光谱和加热过程中的温度升高。与单独的水相比,MWNTs 在水中表现出更高的光吸收。对于相同的激光参数,与单独用激光处理的样品相比,含有 MWNTs 的样品产生了明显更大的温度升高。用人前列腺癌细胞 (PC3) 和鼠肾癌细胞 (RENCA) 用 1064nm 激光照射,辐照度为 15.3W/cm2,照射时间为 1.5 和 5 分钟,单独或与 MWNT 联合照射。用激光加热后的细胞毒性和 HSP 表达来确定单独激光治疗或与 MWNTs 联合治疗的效果。单独的 MWNTs 没有毒性。当与激光辐照联合使用时,MWNTs 的包含显著降低了细胞活力和 HSP 表达。用荧光和透射电子显微镜测量了 MWNTs 与细胞孵育后的细胞内内化。随着孵育时间的增加,在细胞空泡和核中观察到更多的 MWNTs。这些发现为 MWNTs 在癌症治疗中的应用提供了初步的概念验证。