Dually Cross-linked Supramolecular Hydrogel for Cancer Biomarker Sensing.

Lysophosphatidic acid (LPA) as the biomarker of early stage ovarian cancer is essentially difficult to be detected due to lack of target spots. A dually crosslinked supramolecular hydrogel (DCSH) was developed to achieve sensing of LPA, which act 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 insert into the host molecule β-cyclodextrin (β-CD) up to a 1:2 ratio as the competitive interaction mechanism confirmed by 1D NOESY spectroscopy, HRMS, ITC and computational simulation. Our method opens a new strategy to detect biomarkers without target spot and provides a platform for SPR based sensors measuring small molecules.