Semiconducting CuxNi3-x(hexahydroxytriphenylene)2 framework for electrochemical aptasensing of C6 glioma cells and epidermal growth factor receptor

A 2D CuNi metal-organic framework (MOF) named CuxNi3-x(HHTP)2 was synthesized with 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) as the linker and was used as a sensitive scaffold to adsorb aptamer strands for the electrochemical detection of living C6 glioma cells and one of their biomarkers, epidermal growth factor receptor (EGFR). Different from conventional MOFs, the CuxNi3-x(HHTP)2 MOF comprises long-range delocalized electrons, a graphene-analog nanostructure, multiple metal states (Cu0/Cu+/Cu2+ and Ni2+/Ni3+), and abundant oxygen vacancies. With these features, the CuxNi3-x(HHTP)2 MOF anchored a large amount of C6 cell-targeted aptamer strands via coordination among metal centers, oligonucleotides, pi-pi stacking, and van der Waals force. The CuxNi3-x(HHTP)2-based cytosensor showed a low limit of detection (LOD) of 21 cells mL-1 toward C6 glioma cells within a wide range from 50 cells mL-1 to 1 * 105 cells mL-1. Moreover, the proposed aptasensor displayed high selectivity, good stability, acceptable reproducibility, and a low LOD of 0.72 fg mL-1 for detecting EGFR with the concentration ranging from 1 fg mL-1 to 1 ng mL-1. The aptasensor based on the CuxNi3-x(HHTP)2 MOF exhibited superior sensing performance over those based on its monometallic analogues such as Cu3(HHTP)2 MOF and Ni3(HHTP)2 MOF. Hence, this sensing strategy based on a bimetallic semiconducting MOF shows great potential for cancer diagnosis.