Department of Biological Sciences, University of Wisconsin-Whitewater, Whitewater, WI 53190, USA.
Integr Biol (Camb). 2013 Jan;5(1):133-43. doi: 10.1039/c2ib20166f.
Chemically and biologically modified nanoparticles are increasingly considered as viable and multifunctional tools to be used in cancer theranostics. Herein, we demonstrate that coordination of alizarin blue black B (ABBB) to the TiO(2) nanoparticle surface enhances the resulting nanoparticles by (1) creating distinct fluorescence emission spectra that differentiate smaller TiO(2) nanoparticles from larger TiO(2) nanoparticle aggregates (both in vitro and intracellular) and (2) enhancing visible light activation of TiO(2) nanoparticles above previously described methods to induce in vitro and intracellular damage to DNA and other targets. ABBB-TiO(2) nanoparticles are characterized through sedimentation, spectral absorbance, and gel electrophoresis. The possible coordination modes of ABBB to the TiO(2) nanoparticle surface are modeled by computational methods. Fluorescence emission spectroscopy studies indicate that ABBB coordination on TiO(2) nanoparticles enables discernment between nanoparticles and nanoparticle aggregates both in vitro and intracellular through fluorescence confocal microscopy. Visible light activated ABBB-TiO(2) nanoparticles are capable of inflicting increased DNA cleavage through localized production of reactive oxygen species as visualized by plasmid DNA damage detected through gel electrophoresis and atomic force microscopy. Finally, visible light excited ABBB-TiO(2) nanoparticles are capable of inflicting damage upon HeLa (cervical cancer) cells by inducing alterations in DNA structure and membrane associated proteins. The multifunctional abilities of these ABBB-TiO(2) nanoparticles to visualize and monitor aggregation in real time, as well as inflict visible light triggered damage upon cancer targets will enhance the use of TiO(2) nanoparticles in cancer theranostics.
化学和生物修饰的纳米粒子越来越被认为是可行的多功能工具,可用于癌症治疗诊断。在这里,我们证明了茜素蓝黑 B(ABBB)与 TiO(2)纳米粒子表面的配位作用增强了所得纳米粒子的以下特性:(1)产生独特的荧光发射光谱,使较小的 TiO(2)纳米粒子与较大的 TiO(2)纳米粒子聚集体(均在体外和细胞内)区分开来;(2)增强 TiO(2)纳米粒子的可见光激活,以诱导体外和细胞内 DNA 和其他靶标的损伤。ABBB-TiO(2)纳米粒子通过沉降、光谱吸收和凝胶电泳进行表征。通过计算方法对 ABBB 与 TiO(2)纳米粒子表面的可能配位模式进行建模。荧光发射光谱研究表明,ABBB 与 TiO(2)纳米粒子的配位作用可通过荧光共聚焦显微镜在体外和细胞内分辨纳米粒子和纳米粒子聚集体。可见光激活的 ABBB-TiO(2)纳米粒子能够通过局部产生活性氧物种来增加 DNA 断裂,如通过凝胶电泳和原子力显微镜检测到的质粒 DNA 损伤所可视化。最后,可见光激发的 ABBB-TiO(2)纳米粒子能够通过诱导 DNA 结构和膜相关蛋白的改变对 HeLa(宫颈癌)细胞造成损伤。这些 ABBB-TiO(2)纳米粒子的多功能能力能够实时可视化和监测聚集,并在癌症靶标上引发可见光触发的损伤,这将增强 TiO(2)纳米粒子在癌症治疗诊断中的应用。