Synthesis Of Multifunctional Noble Metal Nanozyme And Its Applications In Cancer Diagnosis And Therapy

The pathogenesis of cancer is complicated and the growth rate of cancer cells is fast,so the morbidity and mortality of cancer remain high.Nowadays,tremendous efforts have been poured into developing effective approaches for cancer diagnosis and therapy.Conventional cancer diagnosis methods mainly include CT,magnetic resonance imaging,ultrasound imaging and tumor markers'determination and so on.Common cancer therapies are chemotherapy,radiotherapy,immunotherapy and traditional Chinese medicine treatment.However,traditional diagnostic approaches could not achieve favorable results.Therefore,there is an urgent need to develop an ultrasensitive approach for cancer early detection and multifunctional nanoprobes with good properties.Nanozymes,kinds of nanomaterials possessed enzyme-like property and acted as promising alternatives to nature enzymes,have aroused numerous attentions.Compared with nature enzymes,nanozymes own lots of advantages such ease synthesis,excellent stability and especially regulable catalytic properties.Besides,tumor tisues possess unique microenvironment(TME),in which the cellular metabolism,the p H and the cellular substance content(GSH,H₂O₂,etc.)are greatly different from those in normal tissues.Herein,basing on the specifical microenvironment in tumor sites as well as the unique properties of nanozymes,this thesis presents various appproches for cancer diagnosis and therapy.The main contents are described as follows:1.A sandwich-configuration electrochemiluminescence(ECL)immunosensor based on Au star@BSA-Luminol nanocomplex and PANI-Pt nanozyme for ultrasensitive detection of human chorionic gonadotropin(HCG)has been designed.In this work,nanostructured Polyaniline hydrogels(PANI)decorated with Pt nanoparticles(PANI/Pt)were loaded with numerous capture antibodies to form a primary antibody composite(PANI/Pt-Ab₁);Au star@BSA nanocomposites were used to crosslink HCG detection antibodies and Luminol to generate secondary antibody complex(Luminol-Au star@BSA-Ab₂).Based on the specific sandwiched recognition between antigen and antibody,the above-synthetized Luminol-Au star@BSA-Ab₂complex and PANI/Pt-Ab₁ nanocomposites were attached to the modified sensor.Herein,the used conducting PANI/Pt nanocomposites possessed the unique features,such as large surface area,high electron transfer speed and favorable electrocatalytic activities of hydrogen peroxide,which offered a prominent platform for this sandwich-sensor and acted as efficient ECL signal amplifier also.Under the optimized conditions,the proposed immunosensor exhibited a sensitive detection of HCG in a wide linear range from 0.001–500 m IU m L^-1 with a detection limit of 0.0003m IU/m L(S/N=3).All the results indicated that such a sandwiched HCG immunosensor exhibited favorable ECL analytical performance.This developed method might be potentially used to recognize other clinical proteins in the future.2.Imaging-guided cancaer treatment has aroused tremendous interest owing to visually targeting effect and superior therapy efficacy.In order to combine the merits of nanozymes and the advantages of imaging,carboxylated mesoporous carbon nanospheres with doping small gold nanoparticles(OMCAPs)were synthesized and stabilized with complex of reduced serum albumin and folic acid(r BSA-FA),and finally load IR780 iodide to obtain OMCAPs@r BSA-FA@IR780 nanoprobes.Herein,OMCAPs possessed numerous–COOH groups and large surface area.And loaded NIR dye IR780 could be applied for NIR imaging and be acted as photothermal reagents to enhance photothermal therapy(PTT)effect.Additionally,the small Au NPs embedded in OMCAPs were used as nanoenzyme to catalyze H₂O₂ located in tumor cells to generate reactive oxygen species?OH for synergistic tumor therapy.According to the systematical study in vitro and in vivo,the nanoprobes revealed excellent tumor targeting efficacy,long tumor retention and favorably therapeutic effect,offering an outstanding strategy for other tumors'targeting theranostics.3.Designing cancer theranostic technologies based on tumor microenvironment could significantly improve diagnostic and therapeutic effects of nanoprobes.In this section,we successfully prepared a sequential catalytic platform(Au/Pt star@S-S@r HSA-FA@IR780@GOx)for gastric tumor diagnosis and eradication based on core-shell Au/Pt star after systematically functionalizing L-Cysteine,cystamine dihydrochloride,r HSA-FA composites,IR780 and glucose oxidase(GOx).When the nanoprobes were targeted to the tumor site,the GSH could effectively cleave disulfide linker and release IR780 molecules,which were used for tumor fluorescence imaging,photothermal and photodynamic therapy.The probe could form sequential nanocatalyst integrating the existed Pt nanolayer of Au/Pt star(peroxidase-like catalyst)and the attached GOx(glucose catalyst):GOx could effectively catalyze intracellular glucose to generate H₂O₂by consuming the oxygen and therefore greatly enhance the amount of H₂O₂and acidity for further Fenton-like reaction;The Pt nanolayer could catalyze H₂O₂to produce toxic?OH.Finally,the intelligent Au/Pt star@S-S@r HSA-FA@IR780@GOx probes simultaneously possessed real-time imaging ability and synergetic cancer starving-like therapy/nanozyme oxidative therapy/PTT/PDT feature.