Construction And Drug Release Of Supramolecular Drug Carriers Based On Cucurbiturons And Cyclodextrins

Drug release system is one of the most effective ways to treat cancer.And how to improve the efficacy of chemotherapy drugs and minimize adverse reactions are the focus of current research.In recent years,scientists have developed a variety of functional drug carriers,such as inorganic drug carriers,organic drug carriers and biological drug carriers etc,which can enable sustained and stable drug release to achieve therapeutic effects.However,the existing drug carrier materials still have many disadvantages,such as poor targeting,low loading rate,slow onset and hard degradation.The drug release systems based on supramolecular concept can solve above problems,as they have the advantages of stimulus responsiveness,dynamic reversibility and biological low toxicity,which can not only improve drug loading rate,but also achieve accurate and efficient release at the target site.Based on above research,three kinds of multifunctional supramolecular drug carrier materials based on cucurbit[8]urils（CB[8]）andγ-cyclodextrins（γ-CD）have been designed and synthesized in this dissertation,and the drugs are released under different stimulus,so as to ensure the full effect of drugs,and finally achieve the purpose of treating tumors.pH-sensitive one-dimensional supramolecular nanofibers are successfully constructed by host-guest self-assembly method,with CB[8]as host and tridipyridine/lanthanide complexes as guest.The unique structure of the nanofibers makes them possess the property of CB[8]induced fluorescence enhancement.The solid fluorescence intensity reaches its maximum when the molar ratio of host to guest is 1:1.By adjusting the ratios of different lanthanide ions,green,blueness,white,orange and red multicolor lanthanide luminescence can be exhibited.When the molar ratio of Tb³⁺/Eu³⁺is 1:2,the supramolecular assembly present white fluorescence.In addition,the structure of nanofibers is dissociated under acidic conditions and their size decreases sharply.Hence,they can be used as nanocarriers to load anticancer drug doxorubicin（DOX）,and drug encapsulation rate is 18.76%.The release amount reaches 65.96%after 96 h at p H 5.0 phosphate buffered saline.The cell experiments have proved that DOX-loaded nanofibers are rapidly ingested by cancer cells,and realizing p H-sensitive drug release,giving full play to the drug efficacy.In order to solve the problems of low drug loading of release systems and make them controllable,on the basis of supramolecular nanofibers,photoisomerized group azobenzene derivative and surfactant sodium lauryl sulfonate are introduced,and light-controlled reversible two-dimensional supramolecular nanosheets based on CB[8]are designed.The nanosheets showed excellent lanthanide luminescence performance,and reversible regulation of lanthanide luminescence could be realized by changing light wavelength and time.More importantly,the original 500 nm nanosheets are decomposed into acicular fragments of approximately 5 nm in length and 1 nm in width after irradiating with ultraviolet（UV）light for 10 min,and returned to sheets structure after futher irradiating with 420 nm for 1 min.Therefore,the nanosheets are used as carriers to load hydrophobic drug DOX,which can improve the drug encapsulation rate（46.96%）and realize remote controlled release under UV light.UV and visible light have the disadvantages of high biotoxicity and poor tissue penetration.In contrast,near-infrared（NIR）light have the advantages of high photothermal conversion efficiency,non-invasive and strong tissue penetration,which make them become ideal light source for constructing light-responsive controlled release platforms.Herein,three-dimensional supramolecular hydrogels based onγ-CD are successfully synthesized.The hydrogels possess three-dimensional cross-linked network structure,good stability and self-repairing performance.The reversible phase transition between gel and solution could be triggered repeatedly under NIR irradiation for 30 min and visible light irradiation for 10 min.What’s more,the drug encapsulation rate of supramolecular hydrogels is about 95.94%,and the drug release rate rises to 90%after NIR light irradiating for 4 h.At the same time,the upconversion nanoparticles contained in the hydrogels will produce photothermal action by NIR light irradiation,the tumor therapeutic effect is significantly enhanced through the synergistic effect of chemotherapy and photothermal therapy.