Dually Crosslinked Supramolecular Hydrogel for Cancer Biomarker Sensing

Lysophosphatidic acid (LPA) as the biomarker of early stage ovarian cancer is essentially difficult to detect due to lack of target spots. A dually crosslinked supramolecular hydrogel (DCSH) was developed to achieve sensing of LPA, which acts as a competitive guest molecule triggering the responsive crosslinking of the DCSH. Through this strategy, the surface plasmon resonance combined with optical waveguide spectroscopy could be used to quantitatively detect LPA with a responsive range covering physiological conditions (in pure form as well as mimicking LPA plasma solution) with high selectivity and sensitivity. LPA efficiently immerses into the host molecule β-cyclodextrin (β-CD) up to a 1:2 ratio by the competitive interaction mechanism, confirmed by one-dimensional nuclear overhauser effect spectroscopy (1D NOESY), high-resolution mass spectrometry (HRMS), isothermal titration calorimetry (ITC), and computational simulation. Our method opens a new strategy to detect biomarkers without target spots and provides a platform for surface plasmon resonance (SPR)-based sensors measuring small molecules.