Functionalized Ag/Fe-MOFs nanocomposite as a novel endogenous redox mediator for determination of α2,6-sialylated glycans in serum.

The development of a novel signal amplification system is described for sensitive determination of α2,6-sialylated glycans (α2,6-sial-Gs), an important prognostic tumor biomarker. First, Fe-based metal-organic frameworks (Fe-MOFs) with silver nanoparticles (AgNPs) decorated onto the outer surface were designed and synthesized with controlled octahedron structures. The new Ag/Fe-MOFs nanocomposite possessed strong conductivity and a large surface area to carry more nanoprobes. To connect the Ag/Fe-MOFs nanocomposite with more groups, the nanocomposite was functionalized by -COOH with SH-PEG-COOH to bind with an α2,6-sial-Gs catcher, M-APBA, via -CONH- bonds. More importantly, the Ag/Fe-MOFs also exhibited an excellent endogenous redox mediator property to produce electrons, which is the fundamental mechanism underlying amplification of an electronic signal. A gold electrode was used to accelerate electron transfer and immobilize the α2,6-sial-Gs lectin (SNA). After the sandwich-type catcher recognition (SNA/α2,6-sial-Gs/M-APBA), the current peak response was provoked in the process of oxidizing AgNPs to Ag in the forward anodic potential sweep, while Cl in a PBS solution was transferred into Ag to maintain charge neutrality. Optimized particles were employed for direct fabrication of the sandwich-type affinity biosensor, which was found to show a linear detection range from 1 fg mL to 1 ng mL with a detection limit of 0.09 fg mL. Furthermore, the biosensor exhibited excellent specificity and stability, indicating that such a novel nanobiotechnology platform can be used to initiate potential utility for monitoring biomarkers in serum. (A)Schematic presentation of synthesis and surface modification of Ag/Fe-MOFs. The new Ag/Fe-MOFs nanocomposite possessed commendable conductivity and large surface area to carry more nanoprobe; after functionalizing the Ag/MOFs with SH-PEG-COOH, the functionalized endogenous redox mediator (c-Ag/MOFs) realized the possibility that can connect with the biological catcher. (B) Schematic diagram of electrode construction for detecting α2,6-sialylated glycans (α2,6-sial-Gs). By using the c-Ag/Fe-MOFs functional endogenous redox mediator, we successfully implemented the electrochemical detection of α2,6-sial-Gs.