Design, Synthesis And Self-assembly Of Glucose Functionlized Thermoresponsive Double-hydrophilic Copolymer

In recent years, according to the controllable morphologies, adjustable response temperatureand excellent biocompatibility, thermoresponsive double-hydrophilic polymeric micelles as novelfunctional polymer materials have attracted growing attentions in biomedical material field.Meanwhile, the adding of glycosyl can improve the polymer hydrophilia and reduce thecytotoxicity, so the synthesis and application of glycosyl-based functional polymeric materialshave been favored all over the world.Based on the much research of predecessors, a series of novel thermoresponsive glycopoly-mers based on different thermoresponsive monomers were designed and synthesized via reversibleaddition-fragmentation chain transfer (RAFT) polymerization. The chemical constitutions of themwere confirmed by some technical methods, the thermoresponsive glycopolymer micelles wereobtained using self-assembly technology. Their thermoresponsive properties, protein recognitioncapacity and biocompatibility were investigated systematically.Chapter1presented a detailed review of synthesis and application progress ofPNIPAm-based and PDEGMA-based thermoresponsive polymer, and the research background ofglycopolymers.Chapter2presented the synthesis of thermoresponsive glycopolymers based on differentthermoresponsive monomers by a combination of enzymatic synthesis and reversibleaddition-fragment chain transfer (RAFT) polymerization protocols, and the characterization ofchemical constitution using different technical methods. In order to achieve both bioactivity andthermoresponsibility, a sugar-functionalized monomer6-O-vinyladipoyl-D-glucose (OVAG)prepared by enzymatic synthesis and thermoresponsive monomers N-isopropylacryamide anddiethyleneglycol methacrylate (NIPAm and DEGMA) were used to obtain a serials of novelthermoresponsive glycopolymers such as poly(N-isopropylacryamide–co-6-O-vinyladipoyl-D- glucose) P(NIPAm-co-OVAG), poly(N-isopropylacryamide–co-6-O-vinyladipoyl-D-glucose)-b-poly(N-isopropylacryamide) P(NIPAm-co-OVAG)-b-PNIPAm, poly(diethyleneglycol meth-acrylate-co-6-O-vinyladipoyl-D-glucose) P(DEGMA-co-OVAG) and poly(diethyleneglycolmethacrylate)-b-poly(6-O-vinyladipoyl-D-glucose) PDEGMA-b-POVAG via RAFT polymerize-tion. All the precisely synthesized glycopolymers were characterized by nuclear magneticresonance spectroscopy (1H NMR), Fourier transform infrared spectroscopy (FTIR) and gelpermeation chromatography (GPC). The results showed that the molar ratios of monomer in theresultant glycopolymers were basically consistent with the feed of the monomer ratios;well-defined block glycopolymers with arrow polydispersity (PDI was about1.2) were preparedvia RAFT polymerization; the linear dependence of number-average molecular weight (Mn) ofPDEGMA with the conversion percentage was found, which indicated RAFT polymerization wascontrollable.Chapter3, based on the research of chapter2, presented the fabrication of thermoresponsiveglycopolymer micelles by self-assembling, and revealed the thermoresponsibility andself-assembly mechanism of glycopolymers with different structures. The lower critical solutiontemperature (LCST) of thermoresponsive glycopolymers was studied using UV-visiblespectrophotometer (UV-vis), the LCST values of random glycopolymer P(NIPAm-co-OVAG)were36,37,38oC, the LCST values of block glycopolymer P(NIPAm-co-OVAG)-b-PNIPAmwere33,35.5,36.5oC, the LCST values of random glycopolymer P(DEGMA-co-OVAG) were30,32,36oC, the LCST values of block glycopolymer PDEGMA-b-POVAG was31oC. Overall, theLCST values of glycopolymers increase with increasing molar fraction of OVAG in theglycopolymers. The self-assembly and critical micelle concentration (CMC) were verified byfluorescence spectroscopy with pyrene acting as a hydrophobic probe, the CMC values forP(NIPAm-co-OVAG)-b-PNIPAm and P(NIPAm-co-OVAG) were as low as0.31and0.19g/L,respectively. To obtain average hydrodynamic radius (Rh) and average gyration radius (Rg) atdifferent temperature, the Laser light scattering (LLS) was used combined static laser scattering(SLS) and dynamic laser scattering (DLS). Rhand Rgof thermoresponsive glycopolymer micelleswere depended on the temperature, and the coil-globule transition also was revealed. Micellemorphology of the block glycopolymers was investigated by transmission electron microscopy(TEM), which showed self-assembled micelles with uniform sizes and a regularly spherical shape.The result revealed that thermoresponsive glycopolymers prepared by RAFT polymerization wereable to self-assemble into globose nano-micelles, and the LCST values of glycopolymers could beadjusted precisely. According to this study, biomedical polymer system and application ofglycopolymers were enriched.In the chapter4, we aimed at thermoresponsive glycopolymer micelles fabricated by self-assembling to study the structure effect on protein recognition capacity, the temperatureinfluence on protein recognition capacity, and the cytotoxicity of different materials. The resultsindicated that the sugar moieties in glycopolymers were more and the recognizability to proteinwas greater; the structure was more regular and the recognizability to protein was greater; thetemperature was lower and the random coil structure of glycopolymer micelles were more flexibleto bind lectin, and more sugar moieties were exposed to bind lectin; the glycopolymer micellesolutions had generally very good biocompatibility, but Con A-loaded micelle solution were ableto promote cancer cell death. These results make this study more valuable in the application ofprotein recognition and drug delivery systems.In the chapter5, we summaried the main content in this study, and also look into the future inthis field.