Ultra-small Metal-organic Coordination Nanomaterials For Applications In Photo-theranostics And Acute Kidney Injury Relief

Composed under the coordination between metal ions and functional ligands,metal-organic coordination nanomaterials featured with rich structures and properties,easy compositional adjustments,and inherent bio-metabolism,have captured a lot of concentrations in the study of nanomedicine.As one specific kind of them,ultra-small metal-organic coordination complex nanodots(CCNs)benefited from the ultra-small size,comparing to conventional nanomaterials,exhibited effective renal uptake,which might help the renal excretion of themselves after the disease treatments.Up to now,ultra-small metal-organic CCNs had achieved great outcomes in photo therapy and radiotherapy of cancer,however,the effect of CCNs in other kinds of disease treatments,such as the relief of acute kidney injury,was lack of exploration.Based on that,the main details of this thesis were as follows:Chapter 1:The applications and developments of nanomaterials in biomedicine were described;The principles and applications of some kinds of nanomaterials in photothermal therapy,photoacoustic imaging,and acute renal injury relief were summarized.The synthesis methods,properties,biomedical applications,and metabolism of some metal-organic coordination complex nanomaterials were summarized.Finally,the topic and contents of the thesis were describedChapter 2:Ultra-small ruthenium-phenanthroline(Ru-Phen)CCNs with high NIR absorption and high photothermal conversion efficiency were synthesized.The detailed study of structures,photothermal properties and stability were carried out.After intravenously injecting into tumor-bearing mice,Ru-Phen CCNs could realize highly efficient photothermal treatment of tumor under the guidance of photoacoustic imaging.Based on the ultra-small size,the in vivo metabolism was studied.For the first time,the real-time monitoring of renal clearance was realized by photoacoustic imaging,and this result was further verified by measuring the content of ruthenium in excretions.Ru-Phen CCNs were one outstanding photo-theranostic platform with ultra-small size,high photothermal conversion efficiency and biodegradability.Chapter 3:Natural antioxidants including curcumin(Cur),quercetin(Quer),gallic acid(GA),and proanthocyanidin(PC),were coordinated with low-toxic ferric ions to form ultra-small CCNs(Fe-Cur,Fe-GA,Fe-Quer,and Fe-PC CCNs).It was found that those CCNs exhibited great dispersion and stability in water,and showed strong antioxidative ability.Particularly,Fe-Cur CCNs with the strongest reactive oxygen species(ROS)scavenging ability were utilized for in vivo studies.Owing to the ultra-small sizes,Fe-Cur CCNs showed high kidney uptake after intravenous injection.Remarkably,the oxidative stress induced damage in kidney was significantly ameliorated and the metabolic functions of kidney were well recovered.No obvious toxicity appeared in long-term observation after intravenous injection of Fe-Cur CCNs into mice.Based on that,Fe-Cur CCNs with ultra-small size,high ROS scavenging ability and biocompatibility,were one brand-new and efficient agent for acute kidney injury relief.In this thesis,two kinds of CCNs were synthesized and applied to the study of photothermal therapy,photoacoustic imaging and acute kidney injury relief.Comparing to conventional bio-nanomaterials,the better safety and potential biodegradation of CCNs greatly promoted the future clinic study and transformation.