Synthesis Of Thiol-containing Multidentate Ligand Block Polymer For Surface Functionalization Of Quantum Dots

The semiconductor nanomaterials Quantum Dots(QDs)have attracted a lot of attention because of their unique photochemical and photophysical properties.Compared with traditional organic dyes,QDs have broad absorption spectrum,narrow and symmetrical emission spectrum,strong resistance to photobleaching,high fluorescence efficiency,and so on.Therefore,QDs exhibit great potential in bioimaging,biolabeling,biological detection,and biological tracking.However,QDs,whether synthesized in organic phase and aqueous phase,are all suffering from poor stability in aqueous solutions,especially when they are used in biological field.Our work mostly focused on improving the stability of QDs by modifying the surface of QDs with newly designed thiol-containning multidentate ligand polymers.Moreover,a novel fluorescent nanoprobe based on IgG-functionalized QDs was constructed for the identification and detection of pathogen(Staphylococcus aureus).The contents of this thesis mainly include the following parts:Chapter 1: It was introduced that the property of quantum dots,the synthesis methods,and surface modifications strategies for biological applications.Chapter 2: A thiol-containning multidentate ligand block polymers-polymethacrylic acid-block-polymethacrylic acid mercaptoethyl(P(MAA-b-MEMA))was prepared.A series of thiol-containning multidentate ligand block polymers were synthesized by reversible additionfragmentation chain transfer polymerization(RAFT).With 2-(methacryloyloxy)ethyl disulfanylethanol(MDSE)and methacrylic acid(MAA)as monomer,azobisisobutyronitrile(AIBN)as initiator,and 2-cyano-2-propyldodecyltris trithiocarbonate(CPDT)as chain transfer agent.The chemical structure of P(MAA-b-MEMA)was confirmed by 1H NMR.The polydispersity index(PDI)of P(MAA-b-MEMA)was about 1.1 determined by Gel permeation chromatography(GPC),indicating the living polymerization feature.Secondly,the ultrafiltration stability and the photostability of the CdTe-CdS core-shell QDs modified by thiol-containning multidentate ligand block polymers(P(MAA-b-MEMA))was evaluated.The existence of multiple thiol groups in P(MAA-b-MEMA)can provide multiple binding sites for the surface modification of QDs.So the ultrafiltration stability and the photostability of the P(MAA-b-MEMA)modified QDs was greatly improved by the synergistic effect of multiple thiol groups.Chapter 3: A novel thiol-containning multidentate ligand block polymers-(polyethylene glycol-polymethacrylic acid)-block-polymethacrylic acid mercaptoethyl(P[(EG-MAA)-b-MEMA])was synthesized,with MDSE,MAA and PEGMA as monomer and CPDT as chain transfer agent.A series of thiol-containning multidentate ligand block polymers was synthesized by RAFT.The chemical structure of P[(EG-MAA)-b-MEMA] was confirmed by 1H NMR.The GPC results showed that the average molecular weight of all products was in accordance with the living polymerization feature and the PDI is below 1.2.The morphology and size of CdTe-CdS core-shell QDs modified by P[(EG-MAA)-b-MEMA] was also studied.According to the transmission electron microscopy(TEM),the QDs have uniform morphology without obvious aggregation.Dynamic light scattering(DLS)results showed that the molecular weight of P[(EG-MAA)-b-MEMA] influence the hydrodynamic diameter of modified QDs.Compared with original small molecule mono-thiol ligand modified QDs(MPA-QDs),the stability of P[(EG-MAA)-b-MEMA] modified QDs were significantly improved under different conditions,including pH,high ion concentration,dilution,room temperature,ultrafiltration and UV irradiation.Chapter 4: A immunoglobulin(IgG)functionalized QD nanoprobe(QD-IgG)was constructed for targeted fluorescent imaging of Staphylococcus aureus.IgG was covalently conjugated to P[(EG-MAA)-b-MEMA)]-QD,and electrophoresis was used to verify the linkage of QD to IgG and the optimal conjugation conditions.Then Staphylococcus aureus was incubated with QD-Ig G nanoprobe and fluorescently imaged by laser confocal microscopy.