In Situ Modulating DNAzyme Activity and Internalization Behavior with Acid-Initiated Reconfigurable DNA Nanodevice for Activatable Theranostic

This is the authors' abstract. We don't add key points for this paper.

DNAzyme-mediated gene silencing was still challenged by off-target toxicity. In this study, we developed a split DNAzyme-based nanodevice (sDz-ND) that leveraged acidic tumor microenvironments to drive in situ assembly, thus modulating internalization behavior and silencing activity of DNAzymes. sDz-ND consisted of two different modules, which functionalized with split DNAzyme fragments, respectively. At psychological pH (∼7.4), the two modules were monodispersed, showing cleavage anergy and quenched fluorescence. At pH 6.3, the separated modules could cross-link with each other to form integrated sDz-ND, resulting activation of theranostic function. Meanwhile, the increased particle size and acquired multivalent effect favored 2.1-fold enhanced binding ability, which further facilitated rapid endocytosis of sDz-ND into target cancer cells, then allowing DNAzyme mediated gene silencing. The strategy provides a promising and general concept for precise tumor imaging and gene therapy.