Zhang Chunlei, Wang Kan, Li Chao, Liu Yanlei, Fu Hualin, Pan Fei, Cui Daxiang
Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science & Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, China.
J Mater Chem B. 2014 Oct 28;2(40):6931-6938. doi: 10.1039/c4tb01067a. Epub 2014 Sep 8.
We studied the cytotoxicity of Ag nanoclusters (Ag NCs) capped by the enantiomers l-glutathione (l-GSH) and d-glutathione (d-GSH) synthesized using the mild reduction agent tetrabutylammonium borohydride. The as-synthesized Ag NCs were characterized by HRTEM and UV-visible, photoluminescence and circular dichroism spectroscopy. The circular dichroism spectra of Ag NCs capped with l-GSH and d-GSH showed multiple bands that were identically mirror-imaged, demonstrating that both the metal core and the ligand contributed to the chirality of the GSH-capped NCs. The properties and potential applications of chiral Ag NCs in enantioselective catalysis and chiral recognition and sensing suggest that a comprehensive evaluation should be made of their potential toxicity. We found that Ag NCs capped with d-GSH (AgNCs@d-GSH) were more toxic to both human gastric cancer MGC-803 cells and human gastric mucous epithelial GES-1 cells than Ag NCs capped with l-GSH (AgNCs@l-GSH). Apoptosis also correlated well with the production of reactive oxygen species, mitochondrial membrane depolarization and G/M cell phase arrest in a dose- and chirality-dependent manner. The in vivo injection of AgNCs@l-GSH and AgNCs@d-GSH into mice bearing human gastric cancer xenografts led to a significant reduction in tumor size and increased apoptosis. This knowledge is important from the perspective of understanding the interactions between chiral nanoclusters and cells.
我们研究了用温和还原剂硼氢化四丁铵合成的、由对映体L-谷胱甘肽（L-GSH）和D-谷胱甘肽（D-GSH）包覆的银纳米团簇（Ag NCs）的细胞毒性。通过高分辨透射电子显微镜（HRTEM）、紫外-可见光谱、光致发光光谱和圆二色光谱对合成的Ag NCs进行了表征。用L-GSH和D-GSH包覆的Ag NCs的圆二色光谱显示出多个完全镜像的谱带，表明金属核和配体都对谷胱甘肽包覆的纳米团簇的手性有贡献。手性Ag NCs在对映选择性催化、手性识别和传感方面的性质及潜在应用表明，应对其潜在毒性进行全面评估。我们发现，与用L-GSH包覆的Ag NCs（AgNCs@l-GSH）相比，用D-GSH包覆的Ag NCs（AgNCs@d-GSH）对人胃癌MGC-803细胞和人胃黏膜上皮GES-1细胞的毒性更大。细胞凋亡也与活性氧的产生、线粒体膜去极化以及G/M期细胞阻滞呈剂量和手性依赖性良好相关。将AgNCs@l-GSH和AgNCs@d-GSH体内注射到携带人胃癌异种移植瘤的小鼠体内，导致肿瘤大小显著减小且细胞凋亡增加。从理解手性纳米团簇与细胞之间相互作用的角度来看，这一知识很重要。
