Construction of a human serum albumin site II-targeting supramolecular fluorescent probe for cell imaging and drug delivery

•Two site II-targeting probes were designed with full consideration of their binding to HSA.•TAB2/6 displayed favorable selective HSA sensitivity and strong HSA binding ability.•WP5-TAB2/6 complex inherited the responsiveness and binding ability of the probe.•WP5-TAB2/6 complex self-assembled into a vesicular supramolecular fluorescent probe.•The supramolecular probe could be used for HSA-mediated cell imaging and drug delivery. Two cationic probes (named TAB2 and TAB6) specifically for binding to site II in human serum albumin (HSA) were designed and synthesized. Both probes exhibited selective fluorescence “turn-on” responsiveness to site II in HSA, though minor differences in their cationic terminals resulted in notable variations in their albumin responsiveness. TAB2 and TAB6 also exhibited strong binding affinity toward HSA. The presence of phenylbutazone, ibuprofen, and lidocaine had minimal impact on the albumin responsiveness of these probes. Furthermore, the complex formed by TAB2/6 and water-soluble pillar[5]arene (WP5) showed enhanced HSA site II-targeting fluorescence responsiveness. More importantly, the WP5-TAB2/6 complex self-assembled into vesicular supramolecular probes in aqueous solution (pH=7.4). Those supramolecular probes were promising for HSA-mediated cell imaging and act as a pH-sensitive drug-delivery platform to enhance the anticancer efficiency of doxorubicin (DOX). [Display omitted]