Preparation And Modification Of Novel Micro-nanospheres And Their Applications In The Separation Of Biomacromolecules And Nano-drug Delivery

High performance liquid chromatography(HPLC)has the advantages of fast analysis,high efficiency and high sensitivity.It has become one of the most powerful technologies in separation science.It has widely applications in the fields of chemistry,biology,medicine,environment,food,etc.The column is the key of high performance liquid chromatography,and the separation performance,retention mechanism and column efficiency of the column are affected by the chromatographic stationary phase.Therefore,rational design of high performance column packing has become the focus of chromatographic research.In this paper,combining the advantages of inorganic matrix and organic matrix stationary phase,the preparation and functionalization of porous cross-linked polyglycidyl methacrylate microspheres and the synthesis and functional modification of mesoporous silica microspheres were carried out.The prepared novel chromatographic stationary phase is further used in the field of chromatographic separation.The main work is as follows:1.Monodisperse porous cross-linked polyglycidyl methacrylate microspheres with a particle size of about 7.4 ?m were prepared by an improved two-step seed swelling polymerization method.Using polyallylamine as a bridge,4-bromomethylphenylboronic acid was modified on the surface of polyglycidyl methacrylate microspheres to form a novel liquid chromatography stationary phase.The separation performance of the novel liquid chromatography stationary phase was investigated by using nucleotides and deoxynucleotides as samples,and the stability and repeatability of the chromatographic stationary phase were further explored.2.Monodisperse mesoporous silica microspheres were prepared by polymerization-induced colloidal aggregation.The particle size of Si O2 microspheres was controlled between 3.0?m and 5.5 ?m by changing the content of formaldehyde/urea.Mesoporous silica microspheres with a particle size of 5.5 ?m were used as the chromatographic packing matrix.And the surface of the mesoporous silica microspheres is functionally modified with trichlorooctadecylsilane to introduce a covalently bonded hydrophobic group on the surface of the silica microspheres as a stationary phase.Thereby,the separation of homologues of benzene in liquid chromatography was achieved.The incidence of cervical cancer is gradually becoming younger.Traditional chemotherapeutic drugs have high side effects and low bioavailability.How to design nanomedicines not only can effectively target tumor tissues,but also effectively play the role of drugs,is the key to the development of a new generation of nanomedicine with high therapeutic effect.Covalent attachment of anticancer drugs to water soluble polymers is rapidly becoming one of the most versatile methods of delivering various hydrophobic drugs to specific tumor tissues.The polymer-drug copolymer can overcome the shortcomings of low solubility and stability of the chemotherapeutic drug,short cycle time in the body,large side effects and low efficacy.Using the EPR effect of the tumor,the polymer-drug copolymer can be passively targeted to tumor cells.Hela cells are a kind of cervical cancer cells,which express high esterase,NIH 3T3 cells finely expresses no esterase.In this study,a block copolymer based on polyethylene glycol(PEG)was designed and loaded with dichloroacetic acid via an ester bond to the backbone.HEMA is modified to m PEG by atom transfer free polymerization(ATRP)to facilitate efficient loading of dichloroacetic acid.An esterase-responsive dichloroacetic acid prodrug carrier system was prepared by a combination of a carboxylate bond and dichloroacetic acid.The prepared prodrug carrier was assembled into micelles,and its esterase responsiveness was studied by drug release experiment and cytotoxicity experiment.The nano prodrug carrier can achieve well drug loading and is expected to be applied to cancer treatment.