Construction Of Kidney Scavenging Nanomaterials And Their Application In Disease Diagnosis And Treatment

Cancer and acute kidney injury are major human diseases with a high mortality rate.Early diagnosis of cancer and complete resection of tumors,remission and treatment of acute kidney injury,and significantly reducing the adsorption of non-specific nanoparticles have important value for effective treatment.It is obviously a huge challenge for nanoparticlesloaded drugs to achieve effective accumulation in tumors,acute kidney injury or related lesions,and to rapidly remove them in normal tissues to reduce the toxicity of nanomaterials to the body.At the same time,the development of in vitro detection reagents is of great significance for the detection of early markers of cancer and acute kidney injury.Silver nanoparticles(Ag NPs)and ferric oxide nanoparticles(GS-SPIONs)are widely trusted by researchers because of their good biocompatibility and wide application.Polystyrene microspheres are widely used in early screening of cancer and acute kidney injury markers in vitro due to their large specific surface area and uniform size.This thesis mainly introduces the remission effect of renal clearance of silver nanoparticles and different antioxidant small molecules on acute kidney injury.The application of GS-SPIONs with different particle sizes combined with near-infrared dye indocyanine green(ICG)in tumor fluorescence imaging and renal clearance,as well as the synthesis of in vitro diagnostic reagent-polystyrene microspheres and their application in protein adsorption.The main contents are as follows:1.A kidney-scavenging glutathione(GSH)-coated Ag NPs(GS-Ag NPs)with a diameter of 2 nm was synthesized,and a kidney-scavenging dye-coated TG-Ag NPs was successfully synthesized by coupling 5(6)-carboxytetramethylrhodamine succinimidyl ester(NHSTAMRA)on the surface of GS-Ag NPs through EDC-NHS coupling reaction.By intramuscular injection of glycerol,renal ischemia was caused and endogenous toxic substances were produced to complete the modeling of acute kidney injury in mice.The effects of renal clearance nanomaterials(GS-Ag NPs and TG-Ag NPs)and different antioxidant small molecules on AKI were studied in vitro and in vivo.Comprehensive comparison,β-Tg had the best recovery effect.After 24 hours of administration,BUN recovered to 23.74 mg / dl and CRE recovered to 37.186 μmol / L,both of which were within the normal BUN and CRE indexes of mice,and SOD level was 139 % of normal mice.The half-life of β-Tg in plasma was 0.264 h,and it was cleared out in vitro at a faster rate with high biosafety.Different sizes(3 nm,5 nm,10 nm)of iron oxide nanoparticles(GS-SPIONs)were designed and synthesized,and they were used as carriers to combine near-infrared dye indocyanine green(ICG)through EDC-NHS coupling reaction.The effects of different sizes of Fe3O4 nanoparticles on tumor imaging and renal clearance were studied.The animal in vivo fluorescence imager was used for analysis.After the imaging,the main organs of the mice were imaged and observed to study the in vivo metabolism of iron oxide nanoparticles of different sizes.The results showed that 5 nm and 10 nm ICG-SPIONs nanoparticles were larger and easily taken up by the reticuloendothelial system(RES),which were metabolized from the liver through the intestine,but the circulation time in vivo was significantly stronger than that of ICG.3 nm ICG-SPIONs nanoparticles have a long circulation time in vivo and slow liver metabolism.With the prolongation of circulation time,more nanoparticles accumulate in the tumor due to the high permeability and long retention(EPR)effect of the tumor,and the tumor fluorescence gradually increases.The renal-clearing 3 nm ICG-SPIONs showed excellent tumor imaging.3.Synthesis of in vitro diagnostic reagent polystyrene.Using styrene as the reaction monomer,the effects of initiator content,surfactant type and amount,comonomer content,reaction medium,electrolyte concentration,reaction concentration and other factors on the particle size and polydispersity of polystyrene microspheres were gradually studied.The successful synthesis of polystyrene microspheres was verified by infrared spectroscopy and XPS spectroscopy,and its stability under different concentrations of Na Cl and Zeta potential test were used to verify its stability.Finally,the adsorption capacity of polystyrene microspheres with different sizes for bovine serum albumin was studied.With the increase of the size of polystyrene microspheres,the surface area increases,the electrostatic adsorption sites increase,and the adsorption rate of bovine serum albumin increases.