An intelligent nanodevice based on the synergistic effect of telomerase-triggered photodynamic therapy and gene-silencing for precise cancer cell therapy

Abstract

The development of intelligent and precise cancer therapy systems that enable accurate diagnosis and specific elimination of cancer cells while protecting normal cells to improve the safety and effectiveness of the treatment is still a challenge. Herein, we report a novel activatable nanodevice for precise cancer therapy. The nanodevice is constructed by adsorbing a DNA duplex probe onto MnO₂ nanosheets. After cellular uptake, the DNA duplex probe undergoes telomerase-triggered conformation switching, resulting in a Ce6 “turn-on” signal for the identification of cancer cells. Furthermore, Deoxyribozyme (DNAzyme) is activated to catalyse the cleavage of survivin mRNA, actualizing a precise synergistic therapy in cancer cells involving photodynamic therapy and gene-silencing. The MnO₂ nanosheets provide Mn²⁺ for the DNAzyme and relieve hypoxia to improve the efficiency of the photodynamic therapy. Live cell studies reveal that this nanodevice can diagnose cancer cells and specifically eliminate them without harming normal cells, so making the treatment safer and more effective. The developed DNA-MnO₂ nanodevice provides a valuable and general platform for precise cancer therapy.