Ku Geng, Huang Qian, Wen Xiaoxia, Ye John, Piwnica-Worms David, Li Chun
Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, 1881 East Road, Houston, Texas 77054, United States.
ACS Omega. 2018 May 31;3(5):5888-5895. doi: 10.1021/acsomega.8b00712.
To date, a few studies have investigated the potential use of a short-pulsed laser in selective tumor cell destruction or its mechanism of cell killing. Computer simulation of the spatial and temporal profiles of temperature elevation after pulsed laser irradiation on an infinitesimal point source estimated that the temperature reached its highest point at ∼35 ns after a single 15 ns laser pulse. Moreover, temperature elevation was confined to a radius of sub-micrometer and returned to baseline within 100 ns. To investigate the effect of 15 ns laser pulses on A431 tumor cells, we conjugated hollow gold nanospheres (HAuNSs) to an antibody (C225) directed at the epithelial growth factor receptor. The resulting nanoparticles, C225-HAuNSs, bound to the cell membrane, internalized, and distributed throughout the cytoplasm, with some nanoparticles transported to the vicinity of the nuclear membrane. On using an optical microscope mounted to a tunable pulsed Ti:sapphire laser, rapid and extensive damage of live cancer cells was observed, whereas irradiation of A431 cells pretreated with nontargeted HAuNSs with a pulsed laser or pretreated with C225-HAuNSs with a continuous-wave laser-induced minimal cellular damage. Furthermore, after a single 15 ns laser pulse, C225-HAuNS-treated A431 cells cocultured with 3T3 fibroblasts showed signs of selective destruction. Thus, compared with a continuous-wave laser, shots of a short-pulsed laser were the most damaging to tumor cells that bound HAuNSs and generated the least heat to the surrounding environment. This mode of action by a short-pulsed laser on cancer cells (i.e., confined photothermolysis) may have potential applications in selective tumor cell destruction.
迄今为止，已有一些研究探讨了短脉冲激光在选择性肿瘤细胞破坏中的潜在应用或其细胞杀伤机制。对无限小的点源进行脉冲激光照射后温度升高的空间和时间分布进行计算机模拟估计，在单个15 ns激光脉冲后，温度在约35 ns时达到最高点。此外，温度升高局限于亚微米半径范围内，并在100 ns内恢复到基线。为了研究15 ns激光脉冲对A431肿瘤细胞的影响，我们将中空金纳米球（HAuNSs）与一种针对上皮生长因子受体的抗体（C225）偶联。所得的纳米颗粒C225-HAuNSs与细胞膜结合、内化并分布于整个细胞质中，一些纳米颗粒被转运至核膜附近。使用安装在可调谐脉冲钛宝石激光器上的光学显微镜观察到，活癌细胞受到快速且广泛的损伤，而用非靶向HAuNSs预处理的A431细胞用脉冲激光照射或用连续波激光照射C225-HAuNSs预处理的细胞时，细胞损伤最小。此外，在单个15 ns激光脉冲后，与3T3成纤维细胞共培养的C225-HAuNS处理的A431细胞显示出选择性破坏的迹象。因此，与连续波激光相比，短脉冲激光照射对结合了HAuNSs的肿瘤细胞损伤最大，对周围环境产生的热量最少。短脉冲激光对癌细胞的这种作用模式（即局限光热解）可能在选择性肿瘤细胞破坏方面具有潜在应用。
