Engineering self-catabolic DNAzyme nanospheres for synergistic anticancer therapy

DNAzyme-based gene therapy faces some challenges including cell penetration,activity limitation,and co-delivery functions.Self-assembled DNA nanomedicine has attracted widespread attention due to its many advantages.It is urgent to develop a universal DNA degradation strategy for precise programmable drug release.Herein,we reported a self-catabolic DNAzyme nanospheres(SCNS),which could simultaneously achieve cell penetration,activity enhancement,and co-delivery functions.The SCNS were assembled through Y-DNA stepwise hybridization with each other,which were then loaded with aptamer(Apt),doxorubicin(Dox),and zinc oxide nanoparticles(ZnO NPs).The acid-triggered dissociation of ZnO NPs leads to the generation of Zn^(2+)ions cofactors for immediately self-catabolic DNAzyme nanospheres.After the disassembly of the SCNS,three types of anticancer treatments would be activated,which include Zn^(2+)involved reactive oxygen species(ROS),Dox-induced chemotherapy,and DNAzyme-based gene therapy.The experimental results show that the nanoplatform(Apt-SCNS-Dox-ZnO)has a good tumor-killing effect and minimal side effects.As a smart self-driven drug delivery nanoplatform,it is anticipated to displace extraordinary potential in biomedicine and bioengineering.