Xu Shuang, Li Yan, Chen Zhenjie, Hou Cuilan, Chen Tong, Xu Zhigang, Zhang Xiaoyu, Zhang Haixia
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China.
Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
Mater Sci Eng C Mater Biol Appl. 2016 Feb;59:258-264. doi: 10.1016/j.msec.2015.10.022. Epub 2015 Oct 14.
Mesoporous silica nanoparticles (MSNs) combining gold particles (MSNs-Au) were synthesized as nanocarriers for glutathione (GSH) and pH dual-sensitive intracellular controlled release of the anti-cancer drug doxorubicin (DOX). The MSNs were used as an adsorbent for DOX, and the ultra-small gold nanospheres (Au NPs) partly operated as gatekeepers to control the release of DOX from the pores of MSNs and as the driver of drug release in the presence of GSH due to the association between GSH and Au particles. Under different pH conditions, DOX release changed due to different levels of dissociation between the -SH group on the MSNs and the Au particles. The composition, morphology, and properties of the as-prepared composites were characterized by elemental analysis, fluorescence spectroscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, nitrogen adsorption-desorption, thermal gravimetric and UV-visible spectroscopy. The in vitro release experiments showed that these smart nanocarriers effectively avoided drug leakage in the neutral media. Cytotoxicity and imaging studies also indicated that DOX-loaded Au-MSNs (DOX@MSNs-Au) had a significant inhibitory effect on the growth of Tca8113 cells and sustained the release rate of DOX.
合成了结合金颗粒的介孔二氧化硅纳米颗粒(MSNs-Au)作为纳米载体,用于谷胱甘肽(GSH)和pH双敏感的抗癌药物阿霉素(DOX)的细胞内控制释放。MSNs用作DOX的吸附剂,超小金纳米球(Au NPs)部分充当守门人,控制DOX从MSNs孔中的释放,并在GSH存在时由于GSH与Au颗粒之间的缔合而作为药物释放的驱动因素。在不同的pH条件下,由于MSNs上的-SH基团与Au颗粒之间的解离程度不同,DOX释放发生变化。通过元素分析、荧光光谱、傅里叶变换红外光谱、透射电子显微镜、氮吸附-脱附、热重分析和紫外-可见光谱对所制备复合材料的组成、形态和性质进行了表征。体外释放实验表明,这些智能纳米载体有效地避免了药物在中性介质中的泄漏。细胞毒性和成像研究还表明,负载DOX的Au-MSNs(DOX@MSNs-Au)对Tca8113细胞的生长具有显著抑制作用,并维持了DOX的释放速率。