Laboratory of Pharmacy and Chemistry, and Laboratory of Tissue and Cell Biology, Lab Teaching & Management Center, Chongqing Medical University, Chongqing, 400016, China.
Department of Laboratory Medicine, Affiliated Hospital of North Sichuan Medical University, Nanchong, Sichuan, 637000, China.
Macromol Biosci. 2022 Nov;22(11):e2200248. doi: 10.1002/mabi.202200248. Epub 2022 Sep 1.
Self-assembled DNA nanostructures hold great potentials in biomedical applications. Nevertheless, the negatively charged DNA backbone and susceptivity to enzyme degradation pose challenges to this regard. Engineering the surface properties of DNA nanostructures by assembling DNA with guest molecules in magnesium-free system is promising to solve these issues. In this study, the polyamines-mediated DNA self-assembly with an emphasis on the valency of polyamines is investigated. Both spermine, spermidine, and putrescine can assemble DNA tetrahedron under appropriate concentrations. The cytotoxicity and cellular uptake efficiencies vary with the polyamine valency. Compared with magnesium-assembled DNA tetrahedron, polyamine-assembled DNA tetrahedron exhibits higher cellular uptake efficiency and serum stability. Circular dichroism spectrum results indicate that polyamines induce DNA conformation slightly shifting from B form to A form. The improved performances of polyamine-assembled DNA tetrahedrons under physiological settings are attributed to the surface properties that altered by guest molecules polyamine. The current study suggests that engineering the surface properties of DNA nanostructures by assembling them with guest cationic species is promising to further their biomedical applications.
自组装 DNA 纳米结构在生物医学应用中具有巨大的潜力。然而，带负电荷的 DNA 骨架和易受酶降解的特性给这方面带来了挑战。通过在无镁体系中组装 DNA 与客体分子来工程化 DNA 纳米结构的表面性质，有望解决这些问题。在本研究中，研究了聚胺介导的 DNA 自组装，重点是聚胺的价态。在适当的浓度下，精胺、亚精胺和腐胺都可以组装 DNA 四面体。聚胺的价态影响细胞毒性和细胞摄取效率。与镁组装的 DNA 四面体相比，聚胺组装的 DNA 四面体具有更高的细胞摄取效率和血清稳定性。圆二色光谱结果表明，聚胺诱导 DNA 构象从 B 型略微向 A 型转变。在生理条件下，聚胺组装的 DNA 四面体表现出更好的性能，这归因于客体阳离子物种组装改变了 DNA 纳米结构的表面性质。本研究表明，通过组装客体阳离子物种来工程化 DNA 纳米结构的表面性质，有望进一步推动其在生物医学中的应用。
