Bi-ligand Stabilized Gold Nanoclusters For NIR-Ⅱ Fluorescence Imaging Analysis Of Kidney Injury

In the last decade,kidney disease has become an important public health problem worldwide.Nearly 3 million people in the world are currently suffering from end-stage renal diseases.In the early stage,kidney diseases are usually inconspicuous,but in the late stage they may lead to kidney failure and even patient death.Therefore,early diagnosis and monitoring of kidney diseases are important to maintain the health of the organism.Currently,among the clinical assessment methods of kidney diseases,urine and blood analysis are suffered from low sensitivity;kidney biopsy is highly damaging to the body;magnetic resonance imaging,computed tomography and some other imaging are costly and have the risk of radiation exposure.Fluorescence imaging,especially the second near-infrared(NIR-II)fluorescence imaging,can perform kidney disease diagnosis with low-cost,high-resolution,high-sensitivity,radiation-free and non-invasive.However,the development of NIR-II fluorescence imaging in renal disease research is still limited by the lack of renal-clearable NIR-II luminescent materials with good optical properties.Based on this situation,this study synthesized renal-clearable gold nanoclusters(Au NCs)with NIR-II excitation and emission for the first time.The Au NCs have longer excitation and higher quantum yields than previous developed renal-clearable NIR-II luminescent materials.Their imaging applications have high resolution and signal-tobackground ratio(SBR).The prepared Au NCs can be applied to high-resolution imaging analysis of renal injury induced by renal ischemia-reperfusion and unilateral ureteral obstruction in mice.The main research contents of this thesis include the following two aspects:(1)A series of bi-ligand stabled Au NCs with NIR-II excitation and emission,high quantum yield and good biocompatibility were prepared.Mercaptohexanoic acid mixed with mercaptoethanol,DL-dithiothreitol and cysteamine,respectively,were used as ligands for the synthesis of renal-clearable bi-ligand-stabilized Au NCs.The quantum yields of synthesized Au NCs can reach 1.4%-2.0%,which are about 10 times higher than that of previous renal-clearable NIR-II emission materials.The imaging using the Au NCs showed deep tissue penetration and high resolution under the NIR-II excitation.In addition,in vivo toxicity tests indicated that the prepared Au NCs had a good biocompatibility.Therefore,the developed Au NCs have great application potential in NIR-II biological imaging.(2)Based on the good performance of the prepared bi-ligand stabilized Au NCs,they were further applied to the imaging analysis of kidney injury induced by renal ischemia-reperfusion and unilateral ureteral obstruction in mice.The renal clearance efficiency of Au NCs can reach60%.After the injection of Au NCs into mice,the kidney contour of mice can be clearly imaged.Through the changes of fluorescence imaging signals in the kidney region,the kidney injury induced by renal ischemia-reperfusion and unilateral ureteral obstruction can be imaged and analyzed.The fluorescence imaging with Au NCs to monitoring kidney dysfunction was more sensitive than the clinical method by the measurement of renal filtration markers.The synthesized bi-ligand stabilized Au NCs can imaging analysis of kidney diseases with high sensitivity and high resolution and show a good application prospect in the diagnosis of the kidney diseases.