Signalling probe displacement electrochemical aptasensor for malignant cell surface nucleolin as a breast cancer biomarker based on gold nanoparticle decorated hydroxyapatite nanorods and silver nanoparticle labels

Nucleolin is a multifunctional protein that is markedly overexpressed on the surface of most cancer cells. By taking advantage of the high affinity and specificity of the AS1411 aptamer for nucleolin, a signalling probe displacement electrochemical aptasensor was developed. The thiolated AS1411 aptamer was conjugated to hydroxyapatite nanorods (HApNRs) decorated with gold nanoparticles (AuNPs). To further increase the electrical conductivity of the interface, the ionic liquid 1-ethyl-3-methylimidazolium alanine with its high ion conductivity was placed on the electrode surface. Then, the aptamer was immobilized on the modified electrode and conjugated to signalling c-DNA tagged with AgNPs (c-DNA@AgNPs). In the presence of the MCF7 target cells, the signalling probe is displaced and released from the electrode surface. This leads to a decrease in the current that is proportional to the concentration of cancer cells in the range from 10 to 106 cells mL-1, with a detection limit as low as 8 ± 2 cells mL-1 (n = 3) (based as 3σ/m, where σ is the standard deviation of the blank and m is the slope of the calibration plot). This method presents a promising tool for highly sensitive and selective detection of surface nucleolin on MCF7 cancer cells. Graphical abstract HApNR-AuNP-AS1411 aptamer nanocomposite as an electrochemical sensing interface was immobilized on the gold electrode surface and conjugated to signaling c-DNA tagged with AgNPs for determination of surface nucleolin on MCF7 cancer cells.