Highly selective and sensitive detection of hyaluronic acid based on a pyrene-cored cationic aggregation-induced emission luminogen

Abstract

An aggregation-induced emission luminogen (AIEgen) that is positively charged, compound 1, is synthesized by attaching a pyridyl cation to a pyrene core by use of a cyanoethylene bond. By employing compound 1, it is possible to identify hyaluronic acid (HA) by combining it with the negatively charged HA through electrostatic interactions. When combined with HA, compound 1 exhibits a 9-fold fluorescence enhancement within 7 s, and shows a sensitive and quick response to HA with a detection limit as low as 6.9 ng/mL. Among the variety of available biological substances, even analogues to HA such as chondroitin 4-sulfate (CS) and heparin (Hep), compound 1 is shown to have the most significant fluorescence enhancement when connected to HA only, which demonstrates its excellent selectivity for HA. In particular, upon long-wavelength emission close to 600 nm and an extensive shift (∼160 nm), compound 1 allows for a minimization of the auto-fluorescence interference from complex biological substances and creates more accurate outcomes. Finally, the successful application of compound 1 for the purpose of selective and sensitive detection of HA in living cells is shown to be possible. Notably, good linear relationships arise for a serum assay when the concentration of the applied HA is within the range of 0–8.0 μg/mL (R2 = 0.999), which suggests a possible clinical practice for quantifying HA since the clinical dosage level is covered by this range during both cardiovascular surgery and long-term care. Furthermore, our research offers a feasible and straightforward tool for detecting HA through electrostatic interactions.