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Construction Of Supramolecular System And Performance Study Of Aggregation-induced Emission Component Modified Polymer As Gene Carrier

Posted on:2018-05-03Degree:MasterType:Thesis
Country:ChinaCandidate:Y Z ZhuangFull Text:PDF
GTID:2334330536957385Subject:Medicinal chemistry
Abstract/Summary:PDF Full Text Request
Supramolecular nanoparticles(SNPs)are formed by special noncovalent multivalent supramolecular interactions in a multicomponent system.Compared with traditional polymers,supramolecular polymers whose chains are connected by non-covalent forces such as metal coordination,hydrogen bonding,host-guest interactions,electrostatic forces and so on,could be easily obtained in a facile and dynamic way instead of time-consuming and tedious synthesis as a result of the dynamic and reversible nature of noncovalent forces.Despite of the multifunction of SNPs,insufficient study was performed about the interplay of electrostatics,hostguest interactions in the control of particle size and stability.The systems published before mainly focus on a single force or the synergy effect between electrostatic and host-guest interactions.In this study,we tried to find a balance between repulsive and attractive forces.In this case,stable and biocompatible complexes were expected to be easily obtained instead of time-consuming synthesis.Herein,we utilized ring-opening addition of epoxy groups to generate 4-tert-butylphenyl group(TBP)and ethanediamine(EDA)modified positive charged poly(glycerol methacrylate)(P+TBP).TBP could form inclusion complex with ?-cyclodextrin(CD).Then positively charged or neutral CD grafted poly(glycerol methacrylate)(P+CD/PCD)and negatively charged CD-modified poly(acrylic acid)(PAA-CD)were synthesized and applied to form SNP with P+TBP.P+TBP and P+CD achieved a balance through the attractive host-guest forces and the repulsive electrostatic forces,and form a stable nanoparticle system without the aid of stopper or chemical bonds.The nanoparticles that combine imaging and therapy is advantageous for imaging diagnosis and treatment simultaneously,which has a great demand in the field of tumor treatment.Photodynamic therapy(PDT)is one of the most promising methods in today’s medical and therapeutic platforms.It has many advantages,such as precise controllability,minimally invasive and high accuracy.PDT mechanism is that photosensitizer in the light irradiation produces toxic reactive oxygen species(ROS)which can inhibit or even destroy tumor cells.In this study,we synthesized cationic molecules with aggregation-induced emission(AIE)effect in near-infrared(NIR)to trace the distribution of polymer/DNA complexes in cell and avoid photobleaching effect and aggregation quenching.The cationic polymer including AIE combined with pDNA through electronic forces between positive and negative charge and is used to track its intracellular and in vivo distribution.AIE can also produce ROS.Introducing AIE into the disulfide crosslinked polyethyleneimine polymers modified by tryptophan,can enhance the binding ability to DNA,thus improving the transfection efficiency.
Keywords/Search Tags:Supramolecular, host-guest interaction, gene carrier, AIE, ROS
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