An Intelligent Nanodevice Based on Telomerase-triggered Photodynamic and Gene-silencing Synergistic Effect for Precise Cancer Cells Therapy

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