Acetylcholine Hydrolysis and Antidote Delivery Using a Histidine-Resorcinarene-based Nanocontainer

Abstract

A new nanocarrier was developed for the delivery of an antidote for poisoning with organophosphorus compounds. The nanocarrier acts as an artificial esterase, hydrolyzing acetylcholine and releasing the antidote (atropine) when acetylcholine level is high. The nanocarrier was made using histidine-containing resorcinarene as a building block. Histidine-resorcinarene was preorganized in a microemulsion media and then polymerized with phenylboronic acid, which acts as a linker between the resorcinarene molecules. Antidote (atropine) was incorporated into the nanocarrier with an encapsulation efficiency of 52.2%. At a neutral pH of 7.4, the nanocarrier hydrolyzes acetylcholine to choline and acetic acid. The acid triggers dissociation of the boronate bonds to dissociate, resulting in nanocarrier degradation and the release of 64.4% of the antidote. Transmission electron microscopy (TEM), dynamic and static light scattering (DLS and SLS, respectively), and IR spectroscopy were utilized to characterize the structure of the nanocarriers. Cyclic voltammetry and NMR spectroscopy were employed to evaluate its ability to hydrolyze acetylcholine. Through fluorescence and NMR spectroscopy, it was demonstrated that the nanocarrier could release substrates (fluorescein and atropine) in in response to the presence of acetylcholine.