A pH-responsive hollow mesoporous SiO2 nanocarrier designed for the ultrasensitive detection of alpha-fetoprotein

Effective signal amplification is necessary for the sensitive detection of low-abundance proteins. In this work, a sandwich-type immunosensor for the sensitive detection of alpha-fetoprotein (AFP) was prepared. Hollow mesoporous silica spheres (HMSS) with a large specific surface area and loading capacity were synthesized. Next, their adsorption performance was improved by a hyaluronic acid (HA) coating that could inhibit the escape of lead(ii) ions adsorbed on the hollow silica spheres. After that, an “off–on” strategy was applied to the immunosensor to amplify δ I. The sensitive detection of AFP was obtained by square wave voltammetry (SWV). The antifouling material (HA) not only reduces non-specific binding, but also has good biocompatibility and increases the number of attached secondary antibodies. Finally, we confirmed the successful application of the “off–on” strategy by some electrochemical tests. The final electrochemical sensor has high sensitivity and a low detection limit of 9.9 fg mL−1 (S/N = 3). The proposed “metal ion (organic small molecule)-HMSS@HA” bioresponsive release system has potential application value as a carrier for other electroactive substances.