Cancer cells targeted visible light and alkaline Phosphatase-Responsive TiO2/Cu2+ carbon Dots-Coated wireless electrochemical biosensor

Abstract

The utilization of visible light and pyrophosphates (PPi) accompanied by alkaline phosphatase (ALP) activity-responsive cancer cells-targeting carbon dots using carbonized hyaluronic acid (CD(HA)) by means of electrochemical signals generated from CD(HA)/TiO2/Cu2+-coated surfaces was investigated. The stimuli-responsive surface provided an effective method for wireless sensors under intracellular conditions with an antifouling effect to visualize the cell adhesion interaction with the surface as well as the detection of cancer cells. The highly distinctive intracellular PPi and ALP levels of cancer cells compared to normal cells and CD44 receptor-mediated endocytosis by the CD(HA) chain into cancer cells induced an electrochemical signal change in cell-cultured biosensors detected by electrochemical methods including EIS and a wireless sensing system. The antifouling properties of CD(HA)/TiO2/Cu2+ verified by the time-dependent cell detachment occurring on the modified surfaces in the presence of visible light were employed for the detection of cancer. The resistance of cancer cell-cultured CD(HA)/TiO2/Cu2+ biosensors considerably increased (248 kΩ) as detachment time triggered by visible light irradiation increased compared to normal cells (152 kΩ), which was ascribed to the dissociation of Cu2+ in the system by PPi and ALP in cancer cells and the cellular internalization of CD(HA). With high sensitivity and accuracy for cancer detection by the visible light and enzyme-responsiveness with low LOD value (2.31 cells/mL) on basis of electrochemical approach and 70.05 cells/mL for optical approach, the CD(HA)/TiO2/Cu2+ wireless biosensor offers a promising approach that facilitates cancer diagnosis with antifouling effects to investigate the interaction between cells and modified surfaces.