Acetylcholinesterase Responsive Polymeric Supra-Amphiphiles For Controlled Self-assembly

Stimuli-responsive polymers have captured much attention recently due to theirpotential applications in sensor, biotechnology, drug delivery, etc. Among them,enzyme-responsive polymers have attracted increasing attention, because they showgood biocompatibility, high sensitivity, low toxicity, and easy degradation. Usingenzyme-responsive polymers for studying self-assembly and disassembly has becomea hot point.“Supra-amphiphiles”, a new field of supramolecular chemistry, refers to amphiphilesformed by non-covalent molecular interactions. The combination ofstimuli-responsiveness with supra-amphiphiles opens a new horizon for self-assemblyand disassembly. Stimuli-responsive systems fabricated on the basis of“supra-amphiphile” own many advantages, for example, low cost and easy to befunctionalized.We have fabricated enzyme responsive polymeric supra-amphiphiles by mixing ablock copolymer of poly(ethylene glycol)-block-poly(acrylic acid) withmyristoylcholine chloride in water. The polymeric supra-amphiphiles self-assembleinto spherical aggregates with sizes varying from about35to160nm. Moreover, thespherical aggregates can be disassembled triggered by acetylcholinesterase, anenzyme which can cut off the ester linkage of myristoylcholine chloride.Nile red can be loaded into the spherical aggregates and released in several hoursupon the treatment of acetylcholinesterase. The releasing rate is rather fastconsidering that it takes more than6days for Nile red to diffuse out of the sphericalaggregates without addition of acetylcholinesterase. This is also much faster thanreported works about synthesized enzyme-responsive polymers, which usually takes1~2days for model compound releasing.Acetylcholinesterase is a neural inhibitory enzyme widely found in neural systems. Itis now well known that the abnormal excess of acetylcholinesterase is closely relatedto Alzheimer’s disease and myasthenia gravis. Therefore, it is anticipated that the newenzyme responsive polymeric supra-amphiphile may be explored as a carrier for drug delivery.