Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing University, Nanjing 210023, China.
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
ACS Appl Mater Interfaces. 2021 Oct 13;13(40):47987-47995. doi: 10.1021/acsami.1c15585. Epub 2021 Sep 29.
DNA nanostructures possess unique programmability and addressability and exhibit a wide variety of potential applications. Recently, they demonstrated their ability to be ideal carriers of antibacterial drugs. In this study, the first use of a DNA six-helix bundle (6HB) nanostructure to co-deliver antisense oligonucleotide (ASO) and silver ions is reported. Although 6HB with Ag shows excellent antibacterial effect against both Gram-negative and Gram-positive , 6HB with ASO selectively inhibits . Furthermore, 6HB with both Ag and ASO exhibits enhanced antibacterial efficacy on , probably through two sequential activities. Specifically, Ag-modified 6HB greatly delays bacterial growth by destroying its cell walls, whereas 6HB conjugated with ASO targeting the gene of effectively inhibits its growth in the logarithmic growth phase by inhibiting the expression of the gene. Moreover, this synergistic antibacterial treatment shows excellent biosafety with human normal liver cell L02. This co-delivery system by DNA nanostructures provides a promising platform for antibacterial therapeutics.
DNA 纳米结构具有独特的可编程性和寻址性,并表现出多种潜在的应用。最近,它们展示了作为抗菌药物理想载体的能力。在这项研究中,首次报道了使用 DNA 六螺旋束(6HB)纳米结构共递送反义寡核苷酸(ASO)和银离子。尽管含有 Ag 的 6HB 对革兰氏阴性菌和革兰氏阳性菌均表现出优异的抗菌效果,但含有 ASO 的 6HB 选择性地抑制革兰氏阳性菌。此外,同时含有 Ag 和 ASO 的 6HB 对革兰氏阳性菌表现出增强的抗菌功效,这可能是通过两种连续的作用。具体来说,Ag 修饰的 6HB 通过破坏细胞壁极大地延迟了细菌的生长,而与靶向 基因的 ASO 偶联的 6HB 通过抑制 基因的表达有效地抑制其在对数生长期的生长。此外,这种协同抗菌治疗对人正常肝细胞 L02 具有优异的生物安全性。这种由 DNA 纳米结构实现的共递药系统为抗菌治疗提供了一个有前途的平台。