Study on the Synthesis,Self-assembly,Optical Sensing and Imaging of the Ultrasmall Luminescent Gold Nanoparticles

Author:Zhu Jia Yi

Supervisor:liu jin bin


Degree Year:2019





Luminescent gold nanoparticles(AuNPs)possessed unique properties such as rich optical features,ultrasmall size,the feasibility of surface modification and great biocompatibility,thus these advantages made them become highly attractive in research fields such as sensor,live cell imaging and disease diagnosis.In this thesis a series of luminescent AuNPs with various characteristics and functions,combining their superior physicochemical properties,were constructed to settle the great challenges in detection of heavy metal ions,live cell imaging and biological application of the nanomaterials.The advantages of the AuNPs in various applications and the reaction mechanism were also discussed.Major results were as follows:1.The tetrathiol reagent,pentaerythritol tetrakis 3-mercaptopropionate(PTMP)was employed as both reducing agent and surface coating ligand in the synthesis of 2.4±0.4 nm luminescent PTMP-AuNPs.PTMP also acted as a crosslinker in the formation of a sponge-like network of AuNPs due to thiol-bridging between the ultrasmall PTMP-AuNPs,which resulted in insoluble red-emissive aggregates with maximum wavelength at 675 nm followed by a synergistic hydrophobic effect of the surface ligands.Dispersion of the macroscopic aggregates was enhanced by using a typical surfactant-assisted method under sonication but did not change the morphology of the sponge-like network of PTMP-AuNPs.The as-prepared sponge-like network of AuNPs provided a good reservoir for the heavy metal ions,and showed a saturation capacity of 2.48 g Hg(II)per gram of sorbent due to the synergistic interaction from both the high porosity of the sponge-like structure and the high-affinity metallophilic Hg(II)-Au(I)interaction.In addition,the excellent optical performance of the network along with the specific and strong closed-shell metal interaction led to a sensitive and selective platform for Hg(II)sensing.Therefore,the sponge-like network of PTMP-AuNPs may find potential applications in Hg(II)detection and elimination from drinking water.2.Using a conventional cationic polymer chitosan(CS)with the isoelectric point of 6.5 as template,the self-assembled AuNPs@CS can be easily formed by the ultrasmall luminescent AuNPs,with significantly enhanced cellular interaction and sensitive emission response towards subcellular location.The self-assembled AuNPs@CS become compacted nanostructures(23.5 nm)with high luminescence at low pH values(e.g.,pH<6.5),but reversibly transform to swelled structures with weak luminescence at high pH values(e.g.,pH7.4).The self-assembly of the AuNPs not only improves the emission properties,but also alters the surface charge and assembly size,which result in both enhanced cellular internalization and effective endosomal escape capability.More importantly,the sensitive luminescence response of the AuNPs@CS from the acidic organelle lysosome to the neutral cytoplasm,demonstrates the great potential in optical intracellular tracking.3.The common biomolecules glutathione(GSH)or fetal bovine serum protein(BSA)was employed as both reducing agent and surface coating ligand in the synthesis of ultrasmall luminescent AuNPs.The 600-GS-AuNPs(Emmax 610 nm)were low serum-protein affinity AuNPs.The 800-GS-AuNPs(Emmax 810 nm)were concentration-dependent serum-protein interaction AuNPs and BSA-AuNPs were BSA protected AuNPs.The relationships between pharmacokinetics,biodistribution,excretion pathway,the clearance efficiency and the surface coverage,types of surface ligands of the ultrasmall luminescent AuNPs were investigated.The plasma clearance efficiency of the GS-AuNPs increased with the increasing injection dose,while the BSA-AuNPs exhibited opposite dose-dependent pharmacokinetic properties.The pharmacokinetics of the ultrasmall AuNPs were related to the injection dose,and the correlation was greatly influenced by the type of the surface ligands.Most of the BSA-AuNPs accumulated in reticuloendothelial system.The biodistribution of the concentration-dependent serum-protein interaction 800-GS-AuNPs was significantly affected by the injection dose,whose accumulation in liver,spleen and other tissues gradually increased as the injection dose decreased.Whereas,600-GS-AuNPs with low serum-protein affinity had weak interaction with tissues like liver and spleen,relatively,as indicated by the low body accumulation.The renal excretion and liver metabolism of AuNPs are investigated by biodistribution and optical imaging,respectively.GS-AuNPs with high clearance efficiency,at the high injection dose,were mainly through renal excretion,and at the low injection dose both biliary and renal excretion were employed.The BSA-AuNPs were mainly metabolized by liver with low clearance efficiency.These fundamental understandings of the surface ligand and the injection dose effect on the in vivo metabolism of the ultrasmall AuNPs open up a pathway to maximize their biomedical potential and minimize their toxicity in the future clinical translation.