Study On The Effects Of Surface Modification On The Metabolic Kinetics And Biological Distribution Of Fluorescent Gold Nanoparticles

Due to the small size,biocompatibility,and multifunctional optical properties of gold nanoparticles(AuNPs),they exhibit good potential in biological applications and may become a new type of biological imaging agent.However,before AuNPs can be applied clinically,we must study their metabolism,distribution,and toxic effects in vivo.The distribution and metabolism of AuNPs in the organism are influenced by their size,surface properties,and aggregation state when they are introduced to the biological environment.However,the effects of surface chemistry on the biodistribution of NPs in the body are complex,and little is known about how these characteristics affect their metabolism and distribution in the body.Therefore,exploring the rules that physical and chemical properties affect the metabolism and biodistribution of nanoparticles at the biological level is crucial for designing new types of AuNPs for biosensors and biological imaging.Based on the above research background,this article first synthesized a sulfide dipeptide ligand,and then combined it with other ligands to prepare four types of luminescent AuNPs with different surface chemical properties.The toxic effects of these four luminescent AuNPs on bacteria and cells were further investigated,and their pharmacokinetic and biodistribution in vivo were investigated by mouse models.The details of the study are as follows:(1)Sulfated dipeptide lysine(tDK)was synthesized by a liquid-phase peptide synthesis method.Triphenylmethyl chloride(Trt-Cl)was used to protect the thiol group to prevent any side reactions during the coupling process in the presence of triethylamine.For the preparation of sulfated dipeptide lysine,an organic base:diisopropylethylamine(DIEA)was used as an activator to activate the amino acid,and the sulfated dipeptide was synthesized in the presence of the peptide condensation agent HCTU with a yield of 78.1%.Then,scanning electron microscopy(SEM),nuclear magnetic resonance spectroscopy(NMR),Fourier transform infrared spectroscopy(FTIR),and mass spectrometry(MS)were used to analyze and observe the morphology and chemical structure of the obtained sulfide dipeptide lysine tDK.It was demonstrated that tDK was successfully obtained using glycine sulfide analogues and lysine,and it was found to be a flower shaped spherical particle.(2)Using glutathione(GSH),11-mercaptoundecanoic acid(MUA),thiodipeptide tDY,and the synthesized tDK as encapsulating and reducing agents,four kinds of double ligand luminescent AuNPs were synthesized under light irradiation.Transmission electron microscopy(TEM)was used to observe their microstructure,indicating that the AuNPs were all spherical and uniformly dispersed.The chemical structure and optical properties of the AuNPs were analyzed using FTIR,fluorescence spectroscopy,and fluorescence lifetime characterization.The results show that the ligand successfully binds to the surface of AuNPs,forms an Au-S covalent bond with AuNPs,and AuNPs exhibit good optical properties.XPS spectroscopy confirmed the coexistence of Au(I)and Au(0)in the gold nanoparticles,and the content of Au(I)was found to be closely related to the fluorescence intensity of the AuNPs.(3)In order to understand the toxicity of AuNPs,vitality tests were conducted on bacteria and cells.The results showed that the four synthesized luminescent AuNPs had no significant toxic effects on the viability of bacteria and cells.Then,the effect of surface chemistry of each dual-ligand AuNP type on in vivo biodistribution and pharmacokinetics was investigated using a mouse model.The results showed that changing the surface ligand can have a significant effect on the metabolic kinetics and biodistribution of AuNPs.We observed changes in biodistribution in lung and digestive organs,as well as in blood circulation time.These four AuNPs were mainly distributed in the liver,and small amount of GSH-tDK-AuNPs were found in the intestine.However,MUA modified AuNPs also have a high accumulation in the lungs,which could be attributed to the tendency of MUA-modified AuNPs to aggregate in physiological environments such as PBS solution.Finally,the impact of zeta potential and hydrated particle size of AuNPs on biological distribution was discussed.