Institute of Biochemistry and Biophysics, University of Tehran, P.O. Box 13145-1384, Tehran, Iran.
J Biomed Nanotechnol. 2012 Dec;8(6):968-82. doi: 10.1166/jbn.2012.1451.
The structural changes in DNA caused by the combined effects of silver nanoparticles (Ag NPs) and doxorubicin (DOX) was investigated along with their corresponding inhibitory roles in the growth of T47D and MCF7 cells. The UV-visible titration studies showed that DOX + AgNPs could form a novel complex with DNA and this interaction is in the interface between the value induced by electrostatic and intercalative binding. The values of binding constants revealed that DOX + AgNPs interact more strongly with DNA as compared to Ag NPs or DOX alone. Our CD data revealed that although Ag NPs and DOX alone could alter DNA structure, this combination leads to transition of DNA conformation to an ordered and compact molecular form so called psi-type, considering that DNA is relatively thermally stable in the condition used. Thus, we observed that DOX + AgNPs induces conformational change on DNA. The anticancer property of DOX + AgNPs by MTT assay, DAPI stain and flow cytometry analyses demonstrated that this combination can tremendously diminish proliferation of T47D and MCF7 cells compared to DOX or Ag NPs alone. Furthermore, this combination was comparatively non-toxic towards the human endometrial stem cells proliferation. Collectively, these results reveal that DOX + AgNPs could proffer a novel strategy for the development of promising and efficient chemotherapy agents.
研究了银纳米粒子(Ag NPs)和阿霉素(DOX)的联合效应对 DNA 结构的影响,以及它们在 T47D 和 MCF7 细胞生长中的相应抑制作用。紫外可见滴定研究表明,DOX+AgNPs 可以与 DNA 形成一种新型复合物,这种相互作用位于静电和嵌入结合诱导的结合值之间。结合常数的值表明,与单独的 Ag NPs 或 DOX 相比,DOX+AgNPs 与 DNA 的相互作用更强。我们的 CD 数据表明,尽管 Ag NPs 和 DOX 单独可以改变 DNA 结构,但这种组合会导致 DNA 构象向有序和紧凑的分子形式转变,即所谓的 psi 型,因为在使用的条件下,DNA 相对热稳定。因此,我们观察到 DOX+AgNPs 会诱导 DNA 的构象变化。MTT 测定、DAPI 染色和流式细胞术分析表明,与单独使用 DOX 或 Ag NPs 相比,DOX+AgNPs 对 T47D 和 MCF7 细胞的增殖有很大的抑制作用。此外,与单独的 Ag NPs 相比,这种组合对人子宫内膜干细胞的增殖毒性较小。总之,这些结果表明,DOX+AgNPs 可以为开发有前途和有效的化疗药物提供一种新的策略。