Synthesis Of A Water-soluble Calixarene And Its Application In Drug Delivery

Over the past few decades, cancer has become the main cause of death allaround the world, and researchers in many disciplines have exploited varioustreatment maps，especially for drug delivery systems (DDS). To satisfy the clinicalneeds, enormous efforts have been made to decrease the side effects and enhance thetherapeutic efficacy of anticancer drugs. Supramolecular host compounds, such as,crown ether, cyclodextrin, calixarene, cucurbituril and pillarene, play a significantrole in DDS and supramolecule chemistry. In order to realize the target drug release,a series of external stimuli, i.e., light, temperature, pH changes, ultrasound,competitive binding and enzyme have been employed. Stability, biocompatibilityand avoiding nonspecific cellular uptake are the key issues for ideal drug carriers.Mesoporous silica nanoparticles (MSNs) are recognised as smart nanocontainers fordrug loading and controlled release due to their various excellent characteristics, i.e.,tunable pore sizes, robust storage ability, large surface areas and knownfunctionalization procedures.Compared with other response methods, enzyme activation has shown manyadvantages, i.e., mild activation conditions, sustained release profiles and the highestenzymatic specificity and efficiency. Acetylcholine (ACh), as a neurotransmitter,plays an important role in the sense of restoring impaired functions to a normal andhealthy operational level. The concentration of ACh in the cholinergic synapses willchange remarkably when the mechanisms vary in human bodies, especially inParkinson’s disease (PD) patients. In this dissertation, systematic researches havebeen explored based on MSNs and water-soluble macrocyclic arene compoundscentering on the multi-stimuli responsive and targeted drug release. The majorcontents of this dissertation are as follows：In the first part, two types of biocompatible nanovalves based on sulfonatocalix[4]arene and modified MSNs have been constructed, which containenzyme cleavage sites, one with ester-linked tether and another with urea-linkedtether. The systems can realize drug release from nanocarriers with three differentstimuli types, i.e., competitive binding agent, pH variation and enzyme. It is worthmentioning that only the corresponding enzyme can operate ester and urea chemicalsites, while the unmatched tether-linked system is left intact.In the second part, the acetylcholine-responsive drug release system based onMSNs and sulfonatocalix[4]arene (and carboxylatopillar[5]arene) have beenconstructed. These two systems exhibited different release capability under the sameconcentration of competitive agents. Sulfonatocalix[4]arene-capped nanovalveexhibited a good responsiveness to the concentration change of ACh. Meanwhile,although ACh is a weaker competitor for carboxylatopillar[5]arene-capped system,the release behaviour also can be achieved by enhancing the concentration of ACh.Herein, we took advantage of the characteristics of patients and the properties ofsupramolecular nanovalves to realize the final objective of controlled drug release.