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Synthesis Of Tetraphenylethene-Based Aggregation Induced Emissive Polymers And Their Application In The Gene Delivery System

Posted on:2017-06-28Degree:MasterType:Thesis
Country:ChinaCandidate:X Q HanFull Text:PDF
GTID:2311330485952696Subject:Pharmaceutical engineering
Abstract/Summary:PDF Full Text Request
Due to the properties of simple synthesis,inexpensive,biocompatible,biodegradable,non-immunogenic,non-toxic,and water soluble,the cationic polymers were extensively studied in recent years.In this thesis,two kinds of polymer were firstly synthesized.Poly(glycidyl methacrylate)(PGMA)was synthesized by atom transfer radical polymerization(ATRP),followed by modification with cyclodextrin(CD),ethanediamine(EDA)and guanidine(G).Branched polyethylenimine was also modified with CD.The 1H NMR spectroscopy and FTIR spectroscopy demonstrated the successful synthesis of two polymers.The obtained cartionic polymers were used to form complexes with pDNA by electrostatic interaction.Both polymers can efficiently protect pDNA and formed uniform spherical particles,invested by agarose gel electrophoresis assay and SEM respectively,and showed little cell toxicity and good transfection ability.Besides,the modification of G can efficiently improve the endosome escape and gene transfection efficiency.For the purpose of trafficking the process of gene delivery,we creatively incorporated the aggregation-induced-emission molecular to gene delivery system.Firstly,we synthesized cis-para-boronic acid functioned tetraphenylethene and formed AIE polymer with two different polymers through boronate ester.The obtained AIE polymers were also employed to form the complex with pDNA.Both polymers can efficiently protect p DNA,form much smaller particles and improve the stability of complex.The results of CLSM experiments demonstrated that AIE polymer exhibited better gene delivery ability and even transport pDNA to nuclei.Through the construction of FRET system between dye-labled NBD-DNA and AIE polymer,we can preferably traffic the dissociation process of p DNA and the distribution of vehicle and pDNA in cell under two-photon CLSM,providing a new aproach for the design of multi-functional gene delivery system.
Keywords/Search Tags:Gene Transfection, Poly(glycidyl methacrylate), Polyethylenimine, Aggregation-Induced-Emission, Tetraphenylethene, FRET
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