An AIE luminogen self-assembled nanoprobe for efficient monitoring of the concentration and structural transition of human serum albumin

Monitoring the content and structural transition of human serum albumin (HSA) is valuable for diagnosing hypoalbuminemia and albuminuria and elucidating its transport function, respectively. Herein, we developed a multifunctional and efficient nanoprobe based on the self-assembly of an amphiphilic aggregation-induced emission luminogen, TPNN, for HSA detection and structure monitoring. TPNN molecules formed loose self-assembly in aqueous media and emitted faint fluorescence due to vigorous intramolecular motion. In the presence of HSA, a remarkable fluorescence enhancement accompanied by dissociation of TPNN assembly was observed due to the site-specific binding of TPNN to the middle long-narrow pocket of HSA. This binding blocked the intramolecular motion while producing a sensitive, selective, fast and stable fluorescence turn-on response to HSA, making TPNN assembly suitable for the HSA assay. TPNN assemblies also showed superior selectivity to HSA than bovine serum albumin (BSA) due to the distinct binding modes, and enabled us to distinguish the two homologous proteins. Furthermore, the generated TPNN-HSA complex underwent stepwise fluorescence quenching in the presence of protein denaturants and proteases, which revealed the process and kinetics of HSA unfolding and cleavage. TPNN assembly provides a powerful tool for accurate quantification of HSA in serum and urine and real-time monitoring of HSA structural transition.