Programmable
DNA nanostructure self-assembly offers great potentials in nanomedicine,
drug delivery, biosensing, and bioimaging. However, due to the intrinsically negatively charged
DNA backbones, the instability of
DNA nanostructures in physiological settings poses serious challenges to their practical applications. To overcome this challenge, a strategy that combines the
magnesium-free
DNA self-assembly and functionalization is proposed in this study. We hypothesize that naturally abundant
spermidine may not only mediate the self-assembly of
DNA nanostructures, but also shield them from harsh physiological environments. As a proof of concept,
a DNA nanoprism is designed and synthesized successfully through
spermidine. It is found that
spermidine can mediate the isothermal self-assembly of
DNA nanoprisms. Compared to conventional Mg2+-assembled
DNA nanostructures, the
spermidine-DNA nanoprism complex shows higher thermal stability and better enzymatic resistance than Mg2+-assembled
DNA nanoprisms, and more importantly, it has a much higher cellular uptake efficacy in multiple cancerous cell lines. The internalization mechanism is identified as
clathrin-mediated endocytosis. To demonstrate the suitability of this new nanomaterial for biomedical applications, an mTOR
siRNA, after being conjugated into the complex, is efficiently delivered into
cancer cells and shows excellent gene knockdown efficacy and anticancer capability. These findings indicate that the
spermidine-DNA complex nanomaterials might be a promising platform for biomedical applications in the future.