Design,synthesis And Self-assembly Of Stimuli-responsive Supramolecular Vesicles Based On Water-Soluble Tribenzotriquinacene

Stimuli-responsive supramolecular vesicles can controllably release targeted drugs under the environment of cancer cells,and are ideal smart drug carriers.Fluorescent"visual"modification of such carriers is of great significance for real-time monitoring of drug delivery and release processes.Self-assembly of host-guest supramolecular amphiphilic molecules based on macrocyclic molecules in the water phase is an effective way to construct stimulus-responsive supramolecular vesicles.Tribenzotriquinacene（TBTQ）is a rigid bowl-shaped molecule with a stable internal cavity that can specifically recognize guest molecules as host molecules.In this paper,two different types of supramolecular vesicles are constructed based on water-soluble TBTQ,as follows:（1）Construction of pH-responsive fluorescent supramolecular vesicles and controlled drug release based on water-soluble TBTQ.This study designed and synthesized a water-soluble hexacarboxytribenzotriquinacene derivative TBTQ-C₆as the host,and a tetraphenylethylene（TPE）functionalized single-tailed and tetra-tailed quaternary ammonium salt derivatives G1 and G2,with aggregation-induced luminescence（AIE）effect and dodecyl quaternary ammonium salt G3 without AIE effect as guest molecules.Their host-guest chemistry was studied and the critical micelle concentration（CAC）was measured.When the concentration of the supra-amphiphiles were higher than their CAC,they could self-assemble to form fluorescent supramolecular vesicles with pH response.The obtained fluorescent supramolecular vesicles could efficiently load and pH-responsively release the anticancer drug doxorubicin（DOX）.When the pH of the solution was higher than 7.0,the vesicles showed good stability,whereas,when the pH of the solution was smaller than 7.0,the drug was effectively released with the destruction of the vesicles.At the same time,the unloaded supramolecular vesicles showed strong fluorescence,while with the loading of DOX,the dual-fluorescence-deactivation phenomenon of TPE and DOX occurred.After the release of DOX,the fluorescence showed a recovery trend.Thus,these fluorescent vesicles can visually monitor the drug loading and release processes.Finally,cell uptake and cytotoxicity experiments indicated that the vesicle carriers had low toxicity and did not diminish the inhibitory effect of DOX on cancer cells.Therefore,these supramolecular drug-loaded vesicles with pH response and fluorescence changes showed their good potential applications in cancer treatment.（2）Design,synthesis and self-assembly of multi-stimulus-responsive supramolecular vesicles based on water-soluble TBTQ.This study designed and synthesized a guest molecule G-AZO containing an azobenzene structure,and studied its host-guest chemistry with TBTQ-C₆.When the concentration of host-guest supra-amphiphile was higher than its CAC,supramolecular vesicles were self-assembled in water.The electrostatic effect between the host and guest molecules led the pH response character of the vesicles;and the structure of G-AZO made the vesicles with a photo response function.The experimental results showed that the vesicles had a good"reversibility"with repeated changes in the pH value or the wavelength of light.In addition,the temperature response experiments showed the vesicles were less affected by temperature and had a certain thermal stability.Therefore,this study successfully constructed supramolecular vesicles with pH response and light response.In summary,these studies successfully constructed stimulus-responsive supramolecular vesicles based on water-soluble TBTQ derivative and studied their controlled drug release performance.This thesis not only broadens the field of supramolecular chemistry of TBTQ,but also provides a theoretical basis for the development of novel intelligent supramolecular drug-loading materials.