Cholesterol (CHO) is an essential constituent of human cellular tissues and a crucial activity indicator for the clinical diagnosis and prevention of various diseases. Abnormal CHO levels can lead to various cardiovascular diseases, including coronary heart disease, cerebral thrombosis, and atherosclerosis. Thus, developing simple and effective methods for CHO detection is of great significance. Herein, a novel calix[6]arene-modified photonic hydrogel biosensor (PAAH@SCX6) was developed for naked-eye monitoring of CHO based on supramolecular host-guest interactions between 4-sulfocalix[6]arene (SCX6) and CHO molecules. This sensor was constructed by embedding Fe3O4 colloidal nanocrystal cluster chains into a poly(acrylamide-co-acrylic acid) smart hydrogel (PAAH), followed by incorporation of plentiful SCX6 units into the PAAH via hydrogen bonding interactions. The specific recognition of SCX6 to CHO leads to the volume expansion of the hydrogel, causing a shift in the photonic band gap and a change in the hydrogel's structural color. The sensor demonstrated a linear detection range of 2.83-5.20 mM, covering the typical CHO levels in the human body. Importantly, the PAAH@SCX6 biosensor showed high selectivity and satisfactory stability, making it highly suitable for practical applications. Such a photonic hydrogel-based biosensor provides a convenient, simple, and efficient strategy for visual CHO detection.
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