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 ProDs) 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 ProDs but provide specific metal ions acting as cofactors of the designed DNAzymes. Cellular imaging results demonstrated that ProDs could effectively and simultaneously monitor multiple tumor-related microRNAs 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 acids-based biomedical applications.