Preparation Of Ultrasmall Gold Nanoclusters And Its Preliminary Study In Multimodal Imaging

Purpose:Gold nanoclusters?AuNCs?possess both x-ray attenuation characteristics based on high atomic number and near-infrared fluorescence properties based on the strong quantum confinement effect,which can perform CT and fluorescence bimodal imaging simultaneously.Moreover,lanthanides have been proven to be useful for CT imaging due to high atomic number,which could synergistically enhance CT imaging of gold nanoclusters.In addition,the T1 effect of Gd can generate complementary effect to the speciality of gold nanoclusters that paly high density resolution and sensitive metabolic information.However,the strategy to construct multiple contrast agents often requires complex synthetic steps,and the process of integrating can adversely affect each other's imaging effects.This study aims to achieve a simple and effective combination method with gold nanoclusters and lanthanide elements,which could achieve a synergistic maximization of trimodal imaging effects and explore the importance of early imaging diagnosis.Methods:The Ultrasmall gold nanoclusters?Us-AuNCs?with high-efficiency near-infrared fluorescence and CT dual-modality imaging capabilities was prepared by one-step synthesis method using reducing glutathione?rGSH?as reducing agent and stabilizer.Then,the chelating agent DTPAa was coupled with glutathione by adjusting the pH of the solution via amide reaction using ultrasmall gold nanoclusters as a platform to build the multifunctional nanocomposite?Us-AuNCs@Gd?,which possess excellent CT/NIFR/MRI imaging abilities.Contents:The characterizations of the Us-AuNCs and Us-AuNCs@Gd were analyzed by TEM,DLS,Uv-vis and fluorospectro photometer.Then,the in vitro and in vivo imaging ability and toxicity of two nanocomposite were evaluated.Finally,the biocompatibility and distribution of Us-AuNCs@Gd in vivo was assessed.Results:?1?As the ratio of rGSH/Au³⁺/pH value/temperatures increases,the fluorescence and CT imaging effects of the synthesized AuNCs increases gradually with consistent trend of optimizations.?2?TEM shows that the synthesized AuNCs have a particle size about 1 nm.The Uv-vis absorption spectrum shows AuNCs have two absorption peaks at 370 nm and410 nm.The fluorescence spectra shows that the peak of the AuNCs emission wavelength is around 683 nm at 410 nm excitation.The MTT shows the AuNCs have little cytotoxicity with the appropriate concentration ranges.?3?The TEM of the nanocomposites shows the diameter was uniform and equally distributed.The fluorescence spectrum shows the same near-infrared region compared with the gold nanoclusters.The nanocomposite showed stronger X-ray attenuation characteristics and higher T1 relaxation rate during in vitro cases.MTT cytotoxicity results indicate that the nanocomposite has good biocompatibility at the cellular level.?4?Fluorescence imaging can show the metabolic information of the complex;MRI can clearly show the anatomical information of the living level.Besides,imaging results shows that the nanocomposite can be completely excreted by kidney.Histochemical analysis indicate that the complex has good biocompatibility and have the potential to be used as mutilmodal imaging contrast agents.Conclusions:In our study,the ultrasmall gold nanoclusters?Us-AuNCs?was designed and synthesized to possess both near-infrared fluorescence imaging and CT imaging.Furthermore,the interaction between Au and Gd enhances each other's single-modality imaging capability,which can provides a new idea for the establishment of multimodal imaging platforms in the future.