Smart Probes for Ultrasensitive and Highly Selective Sensing of Homocysteine over Cysteine Based on Multi-Cooperative Effects by Using Gold Nanoparticles

Homocysteine (Hcy) is a biothiol that plays a vital role in many physiological processes and is involved in a variety of diseases. However, it is significantly difficult to discriminate Hcy from cysteine (Cys) due to their similar chemical structures (only one methylene difference) and reactivity. In this study, a novel nanosensor was proposed to discriminate Hcy from Cys with multi-cooperative effects by using gold nanoparticles (AuNPs). The discrimination effect for Hcy originates from the interaction difference of the hydrogen bonding, steric hindrance, and carbon chain length in Hcy and Cys with AuNPs. Under the best conditions, this nanosensor has two unique advantages. Firstly, the sensor exhibits high sensitivity with detection limits of 0.1 μM through naked-eye determination and 0.008 μM through UV-vis spectroscopy analysis. Secondly, the sensor showed superior selectivity for Hcy over the other 16 natural amino acids (biothiol-containing Cys and glutathione (GSH)), and it is the first time to clearly distinguish Hcy from Cys (the Cys concentration is 40 times higher than Hcy). Furthermore, the system was further employed to detect Hcy in human serum, and the result was in agreement with that tested by clinicians via enzymatic assays, with acceptable recovery.