A biologically stable, self-catalytic DNAzyme machine encapsulated by metal-phenolic nanoshells for multiple microRNA imaging

DNAzyme machines play critical roles in the fields of cell imaging, disease diagnosis, and cancer therapy. However, the applications of DNAzyme machines are limited by the nucleases-induced degradation,non-specific binding of proteins, and insufficient provision of cofactors. Herein, protected DNAzyme machines with different cofactor designs(referred to as Pro Ds) were nanoengineered by the construction of multifunctional metal-phenolic nanoshells to deactivate the interferential proteins, including nucleases and non-specific binding proteins. Moreover, the nanoshells not only facilitate the cellular internalization of Pro Ds but provide specific metal ions acting as cofactors of the designed DNAzymes. Cellular imaging results demonstrated that Pro Ds could effectively and simultaneously monitor multiple tumor-related micro RNAs in living cells. This facile and rapid strategy that encapsulates DNAzyme machines into the protective metal-phenolic nanoshells is anticipated to extend to a wide range of functional nucleic acidsbased biomedical applications.