Exosome-tuned MOF signal amplifier boosting tumor exosome phenotyping with high-affinity nanostars

The natural phospholipid structure imparts exosomes with not only cargo protection, but rich sites for coordination with metal-organic frameworks (MOFs) to assemble functional nanocomplexes, such as signal amplifiers. Here, we exploit exosomes to tune MOF signal amplifiers (Exo-MOF) for ultrasensitive phenotyping of tumor-derived exosomes (tExo) based on self-driven coordination assembly and high-affinity nanostars. Exo-MOF leverages the specific coordination interaction between exosome and MOF that cages abundant redox molecules to assemble a super-redox signal amplifier. Moreover, the dispersed immuno-magnetic nanostars, which are assembled with antibodies on the surface of Au nanostars-coated magnetic nanoparticles, allow for rapid capturing of target tExo, addressing the limited mass transfer on electrode surface. Both Exo-MOF and high-affinity nanostars orchestrate the ultrahigh sensitivity (1 particle per 100 μL, higher than that no Exo-MOF by at least 10-fold), specificity and speed of the sensor in tExo detection. Such a sensitive strategy allows profiling tExo across seven cancer types, and revealing the distinct exosomal surface expression patterns. Further, the Exo-MOF sensor accurately distinguishes cancer patients from healthy individuals in a clinical cohort, and provides new opportunities for functional materials assembly and precision diagnostics.