The Construction Of Stimuli-Responsive Supramolecular Nanocarriers Based On Water-Soluble Pillar[5]arene

Macrocyclic host such as crown ethers,cyclodextrins,calixarenes,and cucurbiturils and pillararenes play very important role in the field of supramolecular chemistry.Since been reported in 2008,pillararenes have attracted great attention owing to its highly rigid and symmetrical pillar architecture.So far,various types of supramolecular nanoscale self-assembly aggregates have been constructed by functionalized pillar[n]arenes,which are sensitive to environmental stimuli,and they will play an important role in the construction of nano-materials,chemical sensors,transmembrane channels,and supramolecular polymers.In this dissertation,we investigated the property of a novel type of glucose-responsive smart supramolecular drug delivery system based on water-soluble pillar[5]arene and pyridylboronic acid derivative,which was used for controlled insulin delivery.Furthermore,we designed a target drug delivery system based on functionalized water-soluble pillar[5]arene.This main content consists of the following two parts:In the first part,we constructed a glucose-responsive supramolecular drug delivery system based on the host-guest interaction between a water-soluble pillar[5]arene(WP5)and a pyridylboronic acid derivative(G)for insulin delivery and controlled release at physiological condition,which represents the ideal treatment of diabetes mellitus.The drug loading and in vitro drug release experiments demonstrated that the large molecular weight insulin could be successfully encapsulated into the supramolecular vesicles with high loading efficiency,which to the best of our knowledge,is the first example of small size supramolecular vesicles with excellent encapsulation capacity of large protein molecule.Moreover,FITC-labeled insulin was used to evaluate the release behavior of insulin,and it was demonstrated that high glucose concentration could facilitate the quick release of insulin from insulin-loaded supramolecular nanocarriers,suggesting a smart DDS for the potential application in controlled insulin release only under the hyperglycemic conditions.Finally,we demonstrated that these supramolecular nanocarriers have good cytocompatibility,which is essential for their further biomedical applications.The present study provides a novel strategy for the construction of glucose-responsive smart supramolecular drug delivery system,which might have potential applications for the treatment of diabetes mellitus.In the second part,we designed a target drug delivery system based on functionalized water-soluble pillar[5]arene,which is modified by introducing an anticancer drug doxorubicin via an alkyl chain linker.This functionalized pillar[5]arenes are expected to form prodrug vesicles in water.Meanwhile,we also designed and synthesized a sulfonate guest molecule bearing target group RGD peptide,assuming that it can be decorated on the surface of vesicles through the host-guest interaction between sulfonate guest and water-soluble pillar[5]arene.Follow-up research work is currently underway.