School of Civil and Environmental Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA.
Adv Exp Med Biol. 2014;811:93-109. doi: 10.1007/978-94-017-8739-0_6.
The interaction between nanoparticles (NPs) and DNA plays an important role in the genotoxicity of NPs, and it is imperative to characterize the nano/DNA interactions and explore the underlying chemical mechanisms. In this chapter, we demonstrated systematic experimental approaches based on atomic force microscope (AFM), coupled with modeling computation to probe the binding activity of NPs with DNA and the putative genotoxicity. Using quantum dots (QDs) as a model NP, we examined the binding kinetics, binding isotherm, binding specificity, and binding mechanisms of NPs to DNA with the application of AFM. We further assessed the binding affinity between NPs and DNA by calculating their interaction energy on the basis of Derjaguin-Landau-Verwey-Overbeek (DLVO) models. The modeling results of binding affinity were validated by the NPs/DNA binding images experimentally derived by AFM. The investigation of the relationship between the binding affinity of five NPs ((QDs (+), QDs (-), silver NPs, hematite NPs, and gold NPs) for DNA with their inhibition effects on DNA replication indicated that NPs with a high binding affinity for DNA molecules exhibited higher inhibition on DNA replication. The methodology employed in this study can be extended to study the interaction of other NPs with DNA, which is anticipated to benefit the future design of safe NPs, as well as the toxicological investigations of NPs.
纳米颗粒（NPs）与 DNA 的相互作用在 NPs 的遗传毒性中起着重要作用，因此，必须对纳米/DNA 相互作用进行特征描述，并探索其潜在的化学机制。在本章中，我们展示了基于原子力显微镜（AFM）的系统实验方法，结合建模计算来探测 NPs 与 DNA 的结合活性以及潜在的遗传毒性。我们使用量子点（QDs）作为模型 NP，通过 AFM 研究了 NPs 与 DNA 的结合动力学、结合等温线、结合特异性和结合机制。我们进一步通过基于德热加伦-朗道-维尔贝克（DLVO）模型计算它们之间的相互作用能来评估 NPs 与 DNA 之间的结合亲和力。NP/DNA 结合图像的 AFM 实验结果验证了结合亲和力的模型计算结果。我们研究了 5 种 NPs（（QDs(+)、QDs(-)、银 NPs、赤铁矿 NPs 和金 NPs）与 DNA 结合亲和力与它们对 DNA 复制的抑制作用之间的关系，结果表明，与 DNA 分子具有高结合亲和力的 NPs 对 DNA 复制的抑制作用更高。本研究中采用的方法可以扩展到研究其他 NPs 与 DNA 的相互作用，这有助于未来设计安全的 NPs，并对 NPs 的毒理学研究提供帮助。
