Flourescene Turn-on And Drug Delivery Systems Based On AuNPs For Tumor Imaging And Renal Fibrosis Therapy

As the development of industry and technology and increasing environmental pollution the incidence of various diseases is gradually increasing.Facing the growing threats on public health,it is urgent to exploit high efficient prevention,diagnosis and therapy strategy.In recent years,the cross-over study of nanomaterials and biomedicine has attracted more and more attentions from scientists,owing to the excellent biocompatibility,tunable morphology and property and various surface modification of nanomaterials..Gold nanoparticles?Au NPs?possess,in addition to characteristics above,special optical properties,low nonspecific adsorption and easy surface modification.Thus,AuNPs play important roles in drug delivery,bio-labeling,biological analysis and bio-imaging.Cancer is one of the greatest threatens to public health.Exploiting rapid,high-efficient and non-side-effect diagnosis system is a big challenge in cancer therapy.Recently,fluorescence imaging based on NPs is getting more and more attention and research because of its superiority in early diagnosis and treatment of tumor.However,the biggest barrier for tumor imaging application of NPs is to achieve higher efficient imaging.At the same time,chronic kidney disease?CKD?is another disease with high morbidity and lethality and hard to be healed.Renal fibrosis is a common consequence of CKD,treatment of renal fibrosis can significantly improve state of illness and relieve the progress of nephropathy.Clinically,traditional therapies show limited treatment outcomes as well as severe side effects.In fundamental research area,people focus on using signal path inhibitor to realize fibrosis controlling.But there still have many drawbacks for these strategies,such as inactivation of drug during delivery,non-specific targeting,low efficacy and high cost,which restrict their application toward clinic.Meeting the great challenge in biomedical research and combining the superior physicochemical properties of AuNPs,we prepared AuNPs with different surface coating and optical properties.Based on them,a series of nanocomposites with various characteristics and functions were constructed by self-assembling.Their applications in metal ion detection,tumor imaging and renal fibrosis therapy had been investigated,which provided referable thoughts for designing and developing novel nanomedicines.Major results of this thesis were as follows:1.Fluorescent AuNPs coated with lipoic acid were synthesized,then modified them with glutathione?GSH?to form functional GH-AuNPs.Studies found that GS-AuNPs shown3.5-times stronger fluorescence than AuNPs.Meanwhile,GS-AuNPs had high sensitivity in Cu²⁺specific recognition,which ignored the interference of other metal ions(Fe³⁺,Co²⁺,Ni²⁺,Cr³⁺).Quantitative detection results revealed that it had broad linearity range?3.3-83.3?M?.The highly sensitive and superior interference rejection of GS-AuNPs in Cu²⁺detection made it a promise Cu²⁺detector.2.Near-infrared luminescent AuNPs?LAuNPs?coated with BSA were prepared,then modified LAuNPs with GSH to offer them with rich coordinating groups?LGAuNPs?.A fluorescence turn-on system was constructed through the coordination assembly of LGAuNPs induced by CO²⁺?LGAuNPs-Co?.The assembly presented pH-responded fluorescence turn-on property:under neutral condition,LGAu NPs had coordination interaction with Co²⁺and form assembly structure,whose fluorescence was partly quenched in“off”status;under acidic condition,the coordination bond broke because of the acid effect,whose fluorescence became stronger even regain in“on”status.3.The tumor imaging application of LGAuNPs-Co fluorescence turn-on system was studied.The system was applied on cancer cells and tumor-bearing mice to investigate its biocompatibility,tumor imaging efficiency,biodistribution and pharmaconinetics,which revealed that the LGAuNPs-Co fluorescence turn-on system had excellent biocompatiblebility and tumor imaging efficacy.By parallel comparison with individual LGAuNPs we found that the LGAuNPs-Co fluorescence turn-on system had long half-life,high imaging efficacy?large contrast index?,persistent tumor distinguish period,less normal organ accumulation and renal clearable ability.4.Small size AuNPs were prepared,and loaded Co²⁺,a medicative drug for renal fibrosis,through coordination interaction.The AuNPs-based drug delivery system could specifically target to kidney on one hand,on the other hand,the drug release could be triggered by pH.By applying the AuNPs-based drug delivery system on unilateral ureteral obstruction?UUO?model mice to evaluate its therapy efficiency.Results indicated that compared to free Co²⁺,the AuNPs-based drug delivery system could significantly reduce the toxicity of drug,enhance therapy efficacy and improve renal targeting.