20.625pt'0.625pt-Fluoro-substituted DNA-induced self-assembly strategy for engineering hybrid nanospheres

The physicochemical differences between DNA and other molecules pose a challenge to the construction of DNA based nanostructures. Herein, we propose a straightforward approach for preparing multifunctional DNA-based nanospheres through direct self-assembly of 2'-fluoro-substituted single-stranded DNA (2'F-DNA) with various small molecules. Molecular dynamics simulation revealed that 2'F substitution in DNA can cause the repulsion of adjacent PO(4)(3-)group, leading to local stretching of the DNA structure. Moreover, 2'F substituent induced the regular polarization of H2O nearby F to form the hydration layer, which interrupts inherent interactions among bases. In this way, the bases of 2'F-DNA chain have fewer constraints and more flexibility in conformation, facilitating their non-covalent interactions with other molecules and enhancing the self-assembly capacity of 2'F-DNA. Consequently, 2'F-DNA can bind to more molecules, tending to spontaneously form hybrid DNA nano spheres. Following this approach, a chemo-gene therapy 2'F-DNA/doxorubicin model was designed, showing the significant synergistic anti-tumor therapeutic efficacy. Taken together, this study provides an expandable approach for constructing engineering hybrid nanospheres using DNA and other small molecules, which holds great potential for further biological applications.

Automated summary

This study proposes a straightforward approach for preparing multifunctional DNA-based nanospheres through the direct self-assembly of 2'-fluoro-substituted single-stranded DNA (2'F-DNA) with various small molecules. Molecular dynamics simulation reveals that 2'F substitution in DNA can cause repulsion of adjacent PO(4)(3-) groups, leading to local stretching of the DNA structure. Additionally, the 2'F substituent induces the regular polarization of H2O nearby F to form a hydration layer, which disrupts inherent interactions among bases. This approach allows for the construction of engineering hybrid nanospheres using DNA and other small molecules, holding great potential for further biological applications.