| Drug therapy is one of the most important ways to treat diseases,but many anticancer and antimicrobial agents have the disadvantages of poor water solubility,toxic side effects and poor targeting,which affect their application.Stimuli-responsive supramolecular nano-drug carriers constructed based on host-guest recognition self-assembly can release drugs controllably under the environmental stimulation of the lesion site,which can effectively reduce the toxic and side effects of drugs on normal cells and achieve targeted therapy.At the same time,the introduction of fluorescent groups enables the visual monitoring of drug delivery and release processes,and therefore,it is important to develop stimuli-responsive fluorescent supramolecular nanocarriers.Tribenzotriquinacene（TBTQ）has a non-planar"bowl"structure and is an ideal host molecule.Chitosan（CS）,a natural cationic polysaccharide,is a good biomedical material because of its degradability,biocompatibility and antibacterial properties.In this thesis,water-soluble tribenzotriquinacene hexacarboxylate（TBTQ-C6）was used as the host molecule,and tetraphenylethylene（TPE）-labeled chitosan（CS-TPE）or chitosan quaternary ammonium salt（QCS-TPE）with Aggregation-induced emission（AIE）effect were used as guest molecules to construct p H-responsive supramolecular nanospheres by self-assembly,and their properties were characterized.The details are as follows.（1）Self-assembly study of p H-responsive fluorescent supramolecular nanospheres based on TBTQ-C6 and CS-TPE:We designed and synthesized a new TPE-modified chitosan derivative,CS-TPE.In aqueous solution at p H=5.3,CS-TPE could self-assemble into nanospheres alone or with TBTQ-C6 through host-guest combination to form fluorescent supramolecular nanospheres.Under alkaline stimulation（p H=10.4）,nanospheres formed from CS-TPE amphiphiles or TBTQ-C6（?）CS-TPE supra-amphiphiles disintegrate.However,the CS-TPE nanospheres formed significant accumulation after disintegration,whereas the dispersion of the aggregates was significantly improved after disintegration of the TBTQ-C6（?）CS-TPE supramolecular nanospheres.In addition,the fluorescence of CS-TPE was significantly enhanced by the introduction of TBTQ-C6,and the fluorescence stability was less affected by the p H value.The obtained fluorescent supramolecular nanospheres can efficiently load and p H-responsively release the drug berberine（BE）for the treatment of intestinal diseases.Therefore,the p H-responsive fluorescent supramolecular nanospheres based on TBTQ-C6（?）CS-TPE can be further used to visualize oral drug delivery system studies.（2）Self-assembly study of p H-responsive fluorescent supramolecular nanospheres based on QCS-TPE and TBTQ-C6:We designed and synthesized QCS-TPE with good water solubility in a wide p H range（1～10.4）,and investigated its self-assembly behavior and p H responsiveness with TBTQ-C6 in water.It was found that TBTQ-C6 and QCS-TPE self-assembled to form uniform size nanospheres at p H=7.4 and disintegrated at p H=5.3.And the fluorescence is stronger at p H=7.4,indicating that the supramolecular nanospheres have better fluorescence emission ability in physiological environment.The TBTQ-C6（?）QCS-TPE system showed better water solubility compared to the TBTQ-C6（?）CS-TPE system,and the p H response relationship was significantly different.This system is expected to be further used to visualize anticancer drug carrier studies.In addition,we also investigated the antibacterial properties of QCS-TPE nanospheres and found that QCS-TPE showed significant inhibition of E.coli and S.aureus,and the fluorescence of QCS-TPE changed significantly during the antibacterial process,which can be monitored in real time.Therefore,the TBTQ-C6（?）CS-TPE and TBTQ-C6（?）QCS-TPE supramolecular nanospheres designed and prepared in this thesis are expected to be further used for the visualization of drug carriers,and QCS-TPE has potential applications in antibacterial and bacterial sensing. |
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