DNA折纸用于顺铂与反铂结合行为的可视化研究OA

The geometric configuration of platinum-based anticancer drugs plays a decisive role in determining their DNA binding modes and biological activities.However,direct visualization of such differences at nanoscale remains challenging.Herein,a well-defined two-dimensional rectangular DNA origami(90 nm×60 nm)was employed as a programmable platform to systematically investigate the binding behaviors of cisplatin and transplatin.By combining atomic force microscopy(AFM)and agarose gel electrophoresis,the structural evolution of DNA origami was quantitatively analyzed over a gradient molar ratio range(Origami/Pt=1∶1000-1∶6000).AFM results revealed distinct threshold-dependent structural responses for the two geometric isomers.Cisplatin induced pronounced deformation at a molar ratio of 1∶4000,where the proportion of deformed structures increased to～59%and the average height rised from(2.0±0.3)nm to(2.9±0.6)nm.In contrast,transplatin reached its maximum structural perturbation at a lower ratio of 1∶2000,exhibiting～86%deformation and an increased height of(3.0±0.6)nm.At higher Pt loadings(1∶6000),both systems exhibited partial structural recovery,with deformation ratios decreasing to～11%(cisplatin)and～18%(transplatin),accompanied by reduced heights(～2.2-2.3 nm),indicating a non-monotonic structural response behavior.Consistently,gel electrophoresis showed that the relative mobility reached minimum(～0.8)at the corresponding deformation maxima for each system,confirming the cross-scale agreement between nanoscale morphology and macroscopic migration behavior.The observed differences were attributed to geometry-dependent Pt-DNA coordination modes,which regulated the accessibility of nucleobase binding sites and the extent of crosslinking.These results demonstrated that DNA origami could effectively transduce molecular-level interaction differences into measurable nanoscale structural responses,providing a versatile platform for the visualization and mechanistic investigation of small molecule-DNA interactions.