Surface Regulation Towards NIR-emitting Gold Nanoparticles For Biogenic Amines Sensing And Tumor Imaging

Gold nanoparticles(AuNPs)have attracted great attention in the field of biomedicine such as drug delivering and disease diagnosis owing to its feasibility of surface modification,fine stability and good biocompatibility.The application of luminescent AuNPs in bio-imaging avoids the tedious operation of fluorescence labeling,and with the advantages of non-invasive,real-time and high resolution imaging,has great potential in biological labeling,analyzing,sensing and imaging.The ultrasmall gold nanoparticles(< 3.0 nm)have the optical property of size-independent emission.The optical control towards AuNPs depends on the regulation of their surface chemistry.Surface ligands not only affect the optical properties of AuNPs,but also establish the interfaces between AuNPs and the external environment.However,the fundamental understanding on the surface ligand's role in regulating the luminescence of AuNPs and affecting its biological effects is very limited.Herein,we studied the interaction between surface functionalized AuNPs and exogenous biomolecules with the resulting optical responses by systematically regulating the surface chemical properties of ultrasmall AuNPs.The mechanism of fluorescence response was investigated by combining experimental and theoretical calculations.Moreover,the surface functionalized AuNPs was further applied to the study of in vivo tumor targeting and imaging,the main research contents and results were as follows:By rational designing the surface electrophilicity of ultrasmall AuNPs,we found that the surface chemistry plays an important role in reacting with exogenous electron-rich amine molecules.The electrophilicity of surface ligands determines the adsorption distance between AuNPs and amine molecules,resulting in different degrees of optical response.The strong electrophilic ligands on the surface of AuNPs behave like anchors to provide an efficient passage for the nucleophilic amines approaching the gold surface to complete the direct electron donation.The stimuli-responsive emission sensitivities of the AuNPs toward the amines were in accordance with the electrophilicities of the thiolate surface ligands,as proved by both experimental an theoretical calculations.The amine-induced ratiometric emission response resulted in the formation of a high energy emission(~ 600 nm)in the low surface-covered 810 nm-emitting AuNPs,which is related to the amine concentration.Such a stimuli-responsive emission switched from the single emissive AuNPs to the dual-emissive ones,can be used for real-time monitoring of earlier fish deterioration process.Thus,real-time imaging and sensing of the biogenic amines in the early decay of the glass cat fish and salmon is realized through the optimal design of theAuNPs.The fluorescence responses induced by exogenous substancesand provide new methods for designing novel nanoprobes in quantitative biological analysis,bio-imaging and sensing.The in vivo biological effects of negatively charged AuNPs with different sizes were studied by modifying AuNPs with the same surface ligands.We found that large-sized negative charged AuNPs was was engulfed by macrophages,captured by the reticuloendothelial system(RES),thus lost the tumor-targeting efficiency.However,ultrasmall sized AuNPs still has passive tumor targeting function,and has long circulation time in the blood,which results a high tumor targeting efficiency with long tumor targeting time.Through modifying the surface of ultrasmall AuNPs with sulfonic acid groups,it has strong negative charge and thus repulsive with cell membrane,so that would not endocytosed by macrophages,thus accumulated less in the liver and spleen of mice,and can be excreted out of the body through the liver and kidney.