Advancing DNAzyme Technology in Tumor Treatment

DNAzyme-based gene therapy has received great interest in the treatment of cancer and other diseases. Despite its considerable potential in clinical applications, the in vivo therapeutic efficacy of DNAzymes is still unsatisfactory, mainly due to challenges such as poor stability, inadequate catalytic activity, and insufficient target specificity. With the rapid development of nucleic acid chemistry and nanomedicine, substantial efforts have been dedicated in recent years to designing DNAzyme-based nanoplatforms with enhanced treatment efficacy. In addition, extensive combinations of DNAzymes with other treatment strategies have led to many synergistic therapies with improved therapeutic effects. This review focuses on the advance of DNAzyme-based nanoplatforms in cancer treatment. It first summarizes the solutions proposed in recent years to address each of the key challenges in DNAzyme-based tumor therapy, from the perspectives of DNA sequence design, the construction of organic/inorganic nanosystems, and regulation by environmental factors. Next, it reviews the different categories of combined treatment strategies using DNAzymes in cancer therapy. Finally, future trends as well as suggestions in the field are discussed in detail.