Dually Crosslinked Supramolecular Hydrogel for Cancer Biomarker Sensing

Abstract

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), highresolution 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.

Recent Advances in Host‐Guest Supramolecular Hydrogels for Biomedical Applications

“…The binding of the competitive guest resulted in increased hydrogel swelling with larger layer thickness and decreased refractive index, which could be recorded using combined surface plasmon resonance and optical waveguide spectroscopy (SPR‐OWS). The developed hydrogel sensor demonstrated effectiveness in the detection of lysophosphatidic acid (LPA), the biomarker for ovarian cancer in its early stage, [109] which opens a new window for early‐stage disease diagnosis through detection of small molecule biomarkers.…”

Nanomaterial-based biosensor developing as a route toward in vitro diagnosis of early ovarian cancer

“…Recently, Jie et al. developed a combination of surface plasmon resonance (SPR) and optical waveguide spectroscopy (OWS) to detect LPA with a dual-crosslinked supramolecular hydrogel (DCSH) [ 67 ]. DCSH coated on the gold surface had a tight structure because the polymer network contained β-cyclodextrin and ferrocene groups, where one ferrocene was embedded in two adjacent β-cyclodextrin cavities.…”

Shaping Macromolecules for Sensing Applications—From Polymer Hydrogels to Foldamers

“…Polymeric materials used for sensors are divided into natural hydrogels, derived from natural polymers, e.g., proteins (collagen [ 76 , 80 , 83 ], elastin [ 84 , 85 ], gelatin [ 86 , 87 , 88 ], albumin [ 29 , 89 ]), polysaccharides (hyaluronic acid [ 90 ], alginate [ 91 , 92 , 93 , 94 , 95 ], chitosan [ 82 , 96 , 97 , 98 , 99 , 100 , 101 ], cellulose [ 74 ]), and synthetic hydrogels [ 39 , 102 , 103 , 104 , 105 , 106 ], based on laboratory-made polymers. Hydrogels in sensing applications are often used as a hybrid material, blend of polymers or in composition with inorganic materials, e.g., graphene, graphene oxide, or silica [ 31 ].…”

“…Considering the wide range of characteristics that can be achieved by tuning in both molecular and structural levels and the ability to respond to external stimuli, such as temperature [ 58 , 65 ], light [ 66 ], pH [ 58 , 94 ], ionic strength [ 62 , 127 , 135 ], and the presence of (bio)molecules [ 104 , 136 , 137 , 138 , 139 ], synthetic hydrogels have become important materials for the design and construction of sensors and biosensors in various fields of applications. Different types of synthetic polymer-based hydrogels have been used in sensing, e.g., poly(acrylic acid) [ 40 , 105 , 140 ], poly(ethylene glycol) [ 36 , 39 , 141 , 142 ], poly(ethylene glycol) methacrylate [ 143 ], poly(acrylic acid- co -dimethylaminoethyl methacrylate) [ 144 ], poly(methyl methacrylate- co -methacrylic acid) [ 145 ], polyacrylamide [ 35 , 37 , 77 , 103 ], poly(acrylamide- co -acrylic acid) [ 146 ], poly(N,N-dimethylacrylamide) [ 78 ], poly(N,N-dimethylacrylamide- co -2-(dimethylmaleimido)N-ethyl-acrylamide- co -vinyl-4,4-dimethylazlactone) [ 102 , 106 ], poly(N-isopropylacrylamide- co -2-acrylamido-2-methylpropane sulfonic acid) [ 147 ], poly(vinyl alcohol) [ 81 ], poly(2-hydroxyethyl methacrylate) [ 75 ], and poly(diallyldimethyl ammonium chloride) [ 75 ]. Polymer materials are functionalized with fluorophores, chromophores, or conducting elements to enable readout using relevant detection techniques ( Table 2 ).…”