2D MOF-enhanced SPR detector based on tunable supramolecular probes for direct and sensitive detection of DOX in serum

Therapeutic drug monitoring of doxorubicin (DOX) is important to study pharmacokinetics in patients undergoing chemotherapy for reduction of side effects and improve patient survival by rationally controlling the dose of DOX. A fast and ultra-sensitive surface plasmon resonance (SPR) detector without sample pre-handling was developed for DOX monitoring. First, the two-dimensional metal–organic framework was modified on the Au film to enhance SPR, and then, the supramolecular probes with tunable cavity structure were self-assembled at the sensing interface for direct detection of DOX through specific host–guest interactions with a low detection limit of 60.24 pM. The precise monitoring of DOX in serum proved the possibility of clinical application with recoveries in the range 102.86–109.47%. The mechanisms of host–guest interactions between supramolecular and small-molecule drugs were explored in depth through first-principles calculations combined with SPR experiments. The study paves the way for designing facile and sensitive detectors and provides theoretical support and a new methodology for the specific detection of small molecules through calixarene cavity modulation. Graphical abstract