El-Sayed Ivan, Huang Xiaohua, Macheret Fima, Humstoe Joseph Oren, Kramer Randall, El-Sayed Mostafa
Department of Otolaryngology- A-730, Head and Neck Surgery, University of California at San Francisco Comprehensive Cancer Center, 400 Parnassus Ave, Box 0342, San Francisco, CA 94143, USA.
Technol Cancer Res Treat. 2007 Oct;6(5):403-12. doi: 10.1177/153303460700600505.
Due to the strong surface fields of noble metal nanoparticles, absorption and scattering of electromagnetic radiation is greatly enhanced. Noble metallic nanoparticles represent potential novel optical probes for simultaneous molecular imaging and photothermal cancer therapy using the enhanced scattering and absorption of light. Further, gold nanoparticles can affect molecular fluorescence via chemical, electronic, or photonic interactions. Live cells generate fluorescence due to intracellular and extracellular molecules. Differences in the biochemical composition between healthy and malignant cells can be exploited in vivo to help identify cancer spectroscopically. The interaction of gold nanoparticles with cellular autofluorescence has not yet been characterized. We hypothesized that gold nanoparticles delivered to live cells in vitro would alter cellular autofluorescence and may be useful as a novel class of contrast agent for fluorescence based detection of cancer. The fluorescence of two fluorophores that are responsible for tissue autofluorescence, NADH and collagen, and of two oral squamous carcinoma cell lines and one immortalized benign epithelial cell line were measured in vitro. Gold nanoparticles of different shapes, both spheres and rods, quenched the fluorescence of the soluble NADH and collagen. Reduction of NADH fluorescence was due to oxidation of NADH to NAD+ catalyzed by gold nanoparticles (results we previously published). Reduction of collagen fluorescence appears due to photonic absorption of light. Furthermore, a mean quenching of 12/8% (p<0.00050) of the tissue autofluorescence of cell suspensions was achieved in this model when nanospheres were incubated with the live cells. Gold nanospheres significantly decrease cellular autofluorescence of live cells under physiological conditions when excited at 280nm. This is the first report to our knowledge to suggest the potential of developing targeted gold nanoparticles optical probes as contrast agents for fluorescence based diagnoses of cancer.
由于贵金属纳米颗粒具有很强的表面场，电磁辐射的吸收和散射会大大增强。贵金属纳米颗粒是潜在的新型光学探针，可利用增强的光散射和吸收同时进行分子成像和光热癌症治疗。此外，金纳米颗粒可通过化学、电子或光子相互作用影响分子荧光。活细胞因细胞内和细胞外分子而产生荧光。健康细胞和恶性细胞之间生化组成的差异可在体内加以利用，以帮助通过光谱法识别癌症。金纳米颗粒与细胞自发荧光的相互作用尚未得到表征。我们假设，体外递送至活细胞的金纳米颗粒会改变细胞自发荧光，并且可能作为一类新型造影剂用于基于荧光的癌症检测。在体外测量了负责组织自发荧光的两种荧光团（NADH和胶原蛋白）以及两种口腔鳞状癌细胞系和一种永生化良性上皮细胞系的荧光。不同形状的金纳米颗粒，包括球形和棒状，均可淬灭可溶性NADH和胶原蛋白的荧光。NADH荧光的降低是由于金纳米颗粒催化NADH氧化为NAD⁺（这是我们之前发表的结果）。胶原蛋白荧光的降低似乎是由于光的光子吸收。此外，在该模型中，当纳米球与活细胞一起孵育时，细胞悬液的组织自发荧光平均淬灭了12/8%（p<0.00050）。在280nm激发时，金纳米球在生理条件下可显著降低活细胞的自发荧光。据我们所知，这是第一份表明开发靶向金纳米颗粒光学探针作为基于荧光的癌症诊断造影剂潜力的报告。
