Multifunctional Nano-systems Based On Gold Nanoparticles And Their Applications In Tumor Diagnosis And Therapy

Gold nanoparticles(Au NPs)for CT imaging and radiosensitization based on X-ray characteristics are still lack of effective and precise evaluation,thus limiting the clinical application of Au NPs for X-ray-based tumorous diagnosis and therapy.Moreover,there are still challenges for nanotheranostics to efficiently integrate multiple diagnostic and therapeutic strategies on a single particle with low cytotoxicity via simplified and effective methods.In this dissertation,we report that Au NPs have great size-dependent enhancements on CT imaging as well as radiotherapy(RT)in the size range of 3-50 nm.Based on the optimal-sized gold nanoparticles combining other functional nanoparticles,multifunctional nanosystems were successfully fabricated for tumorous theranostics.The details are as follows:1.Controllable preparation of spherical gold nanoparticles with seven particle size within 3-50 nm range.The results showed that the seed growth preparation method possess good repeatability.There was a significant difference between particle sizes which had good monodispersity.PEG-modifed gold nanoparticles had better temperature stability,p H stability and colloidal stability with low cytotoxicity;2.Size-dependent effect of gold nanoparticles for X-ray characteristics.The results showed that different particle sizes endowed gold particles different CT contrast enhancement,the absorbed dose,relative electron density and cellular radiosensitization,which had similar variations.13.2 nm sized gold nanoparticles could simultaneously possess superior CT contrast enhancement and radiosensitization properties;3.Evaluations and theoretical studies of size-dependent effect by Monte Carlo simulations.The results showed that simulation model fabricated by Monte Carlo methods could represent the reality of mixture characteristics for gold nanoparticles solutions.Under Ke V and Me V energy of X-ray radiation,photon fluence and absorbed dose indicated similar variations with simulated particle sizes.Gold nanoparticles sized within 10-14 nm gold particles could simultaneously have significant radiation attenuation and absorbed dose,and here we proposed the corresponding hypothesis and interpretation;4.Optimized gold nanoparticles and X-ray theranostic applications.The resultsshowed that gold nanoparticles with optimal sizes at 13.2 nm could possess good biological safety,effectively tumor passive-targeting ability,and long circulating time in vivo,which could simultaneously achieve enhanced CT imaging and radiotherapy,and their efficacy was much better than that of clinical imaging agent-iodine and clinical radiosensitizer-glycididazolum natrium;5.Multifunctional nanotheranostics based on the optimized gold nanoparticles.The results showed that integrating gold nanoparticles optimal-sized at 13.2 nm with prussian blue nanoparticles could contrust a kind of multifunctional nanosystem with core-shell structure(CSNPs).Particle size of CSNPs was about 138 nm,and CSNPs could realize multimodal imaging of T1/T2-weighted MRI and CT.The combination of PTT and RT induced by CSNPs resulted in remarkable synergistic effect to achieve almost complete eradication of tumors without visible recurrence;All of the results suggest that gold nanoparticles can be used as a kind of platform on the basis of X-ray characteristics to develop multifunctional nano-systems,which may be promising nanotheranostics for tumor diagnosis and therapy applications.