Carbon Nanocage/Fe3O4/DNA-Based Magnetically Targeted Intracellular Imaging of Telomerase via Catalyzed Hairpin Assembly and Photodynamic-Photothermal Combination Therapy of Tumor Cells.

Abstract

Human telomerase has been identified as a potential tumor biomarker for early cancer diagnosis and cancer progression monitoring. We construct a novel magnetic targeting carbon nanocage/Fe3O4/DNA (CNC/Fe3O4/DNA) nanoprobe for intracellular imaging of telomerase via the signal amplification strategy catalyzed hairpin assembly (CHA) and for photodynamic-photothermal therapy of tumor cells. Telomerase primer DNA, trigger DNA, hairpin DNA1 (H1), and hairpin DNA2 (H2) were adsorbed to the surface of CNC/Fe3O4 nanoparticles (CNC/Fe3O4 NPs), and the fluorescence of (chlorin e6) Ce6 was quenched by CNC/Fe3O4 NPs. After entering the living cell through magnetic targeting, the telomerase primer DNA can be extended in the presence of highly activated telomerase, leading to the issue of trigger DNA, which can initiate the CHA cycling process followed by the amplification of the fluorescence intensity. The in vitro detection results justified that the proposed nanoprobe showed good sensitivity and selectivity for telomerase. Confocal microscopy studies indicated that such a nanoprobe can be used to detect the activity of telomerase in living cells and the fluorescence signal was stronger under the guidance of a magnetic field. We successfully employed this nanoprobe to monitor the dynamic activity of telomerase in various types of tumor cells and normal cells and to damage tumor cells by photodynamic-photothermal combination therapy, which evidenced that this is a promising biological method for early cancer diagnosis and tumor cell therapy.