Abstract
AbstractThe development of artificial receptors that combine ultrahigh‐affinity binding and controllable release for active guests holds significant importance in biomedical applications. On one hand, a complex with an exceedingly high binding affinity can resist unwanted dissociation induced by dilution effect and complex interferents within physiological environments. On the other hand, stimulus‐responsive release of the guest is essential for precisely activating its function. In this context, we expanded hydrophobic cavity surface of a hypoxia‐responsive azocalix[4]arene, affording Naph‐SAC4A. This modification significantly enhanced its aqueous binding affinity to 1013 M−1, akin to the naturally occurring strongest recognition pair, biotin/(strept−)avidin. Consequently, Naph‐SAC4A emerges as the first artificial receptor to simultaneously integrate ultrahigh recognition affinity and actively controllable release. The markedly enhanced affinity not only improved Naph‐SAC4A′s sensitivity in detecting rocuronium bromide in serum, but also refined the precision of hypoxia‐responsive doxorubicin delivery at the cellular level, demonstrating its immense potential for diverse practical applications.
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