Multifunctional DNA nanoprobe for tumor-targeted synergistic therapy by integrating chemodynamic therapy with gene silencing

Due to the high complexity, diversity and heterogeneity of tumor occurrence and development, multi-mode synergistic therapy is more effective than single treatment modes to improve the antitumor efficacy. Also, multifunctional probes are crucial to realize synergistic therapy. Herein, a multifunctional DNA tetrahedron nanoprobe was ingeniously designed to simultaneously achieve chemodynamic therapy (CDT) and gene silencing for synergistic antitumor. The multifunctional DNA tetrahedron nanoprobe, DNA tetrahedron-silver nanocluster-antagomir-21 (D-sgc8-DTNS-AgNCs-Anta-21), integrated a CDT reagent (DNA-AgNCs) and miRNA-21 inhibitor (Anta-21) with a specific recognition probe (aptamer). After targeted entry in cancer cells, D-sgc8-DTNS-AgNCs-Anta-21 silenced endogenous miRNA-21 by Anta-21 and produced highly toxic OH by reacting with H2O2, which induced apoptosis in the tumor cells. The targeted recognition of aptamers led to the concentration-dependent death of HeLa cells. On the contrary, the cell survival rate of normal cells was basically unaffected with an increase in the concentration of D-sgc8-DTNS-AgNCs-Anta-21. Therefore, the diverse functions, biocompatibility and programmability of DNA provide a useful and easy way to assemble multifunctional probes for synergistic therapy.

Automated summary

Due to the complexity and heterogeneity of tumors, multi-mode synergistic therapy is more effective than single treatment modes. In this study, a multifunctional DNA tetrahedron nanoprobe (D-sgc8-DTNS-AgNCs-Anta-21) was designed to achieve chemodynamic therapy (CDT) and gene silencing for synergistic antitumor. The nanoprobe silenced miRNA-21 and induced apoptosis in tumor cells through the production of highly toxic OH. The targeted recognition of aptamers resulted in the death of HeLa cells, while normal cells were unaffected. The diverse functions and programmability of DNA provide a useful way to assemble multifunctional probes for synergistic therapy.