Application Of Functionalized Noble Metal Nanomaterials In Tumor Diagnosis And Therapy

Cancer（malignant tumor）is one of the diseases that seriously threaten human health and life.Early detection,early diagnosis and treatment are important means to reduce the mortality rate of patients,prolong the survival time of patients and improve the quality of life.The development of new diagnostic techniques and treatment methods is an important way to seek breakthroughs.Due to their excellent physical and chemical properties,nanomaterials show attractive application prospects,providing new ideas for cancer diagnosis and treatment.Among them,noble metal nanomaterials have the advantages of size-dependent localized surface plasmon resonance（LSPR）,easy surface functionalization,high loading rate and excellent biocompatibility.It has shown broad theoretical research and commercial application value in other fields.Unfortunately,considering that the retention time of precious metals in the body may increase the hidden danger of toxicity,the lack of sufficient research on its metabolic process,and the possible side effects during the treatment process,there is no clinically approved drug for cancer diagnosis and treatment of noble metal nanomaterials.Based on the above considerations,the conditions and performance characterization of multifunctional noble metal nanomaterials were discussed in this thesis,and they were used in tumor multimodal imaging diagnosis and anticancer/antibacterial therapy.First,by preparing ultra-small-sized bimodal probes that can pass through the kidneys and be completely cleared within a reasonable time,thereby reducing the retention of noble metal nanomaterials in vivo.Second,building a multifunctional nanomedicine platform.By combining a drug platform responsive to the tumor microenvironment,the low utilization rate and possible toxicity caused by off-target are reduced,and the nanoscale precious metal materials are accurately delivered to the target tissues and cells,thereby improving the therapeutic effect of tumors.Third,through photothermal/light Dynamic combination therapy not only improves the anti-tumor efficacy,but also reduces the dose of the drug to further avoid damage to healthy tissues.Fourth,it can prevent possible side effects and recurrence and metastasis during the treatment process,reduce complications and infections,so as to achieve increased treatment efficiency.The specific work content is as follows:（1）Here,we fabricated ultra-small and metabolizable dual-mode imaging probes Au/Gd@FA NCs by a facile hydrothermal method for fluorescence/MRI imaging of breast cancer cells and tissues.The ultra-small-sized Au clusters exhibited good near-infrared fluorescence properties,and the doped Gd element enabled the probe to generate T₁ NMR signals.More interestingly,in vivo experiments we found that Au/Gd@FA NCs were excreted in feces after imaging and did not affect the normal physiological metabolism of mice.These results further confirmed the good biosafety of the probe.More importantly,the intracellular reactive oxygen species（ROS）content of Au/Gd@FA NCs and tumor cells was significantly increased under 660 nm laser irradiation,indicating that the probe can promote the production of intracellular ROS and effectively induce cell apoptosis.（2）To improve the therapeutic effect of tumors,we constructed a pH-responsive multifunctional nano-delivery platform AIZH（Au/Ag NRs+ICG@ZIF-HA）.The metal-organic framework（ZIF-8）in this probe can fully respond to the lower pH in the tumor microenvironment to achieve efficient and highly targeted drug delivery.After the release of small-sized Au/Ag NRs and ICG,the combined treatment of photodynamic and photothermal was realized under the stimulation of laser irradiation（808 nm,1.5 W/cm²）.More importantly,ICG can not only convert light energy into ROS to kill tumor cells,but also etch down the Ag shell on the surface of Au/Ag NRs,preventing possible bacterial infection during photothermal therapy.In vivo experiments,we found that the size of mouse tumors can be effectively reduced after AIZH injection via the tail vein and orthotopic.And compared with the control group,the mice treated with this platform had significantly less skin surface damage.（3）During the course of tumor photothermal therapy,it is easy to cause a certain degree of thermal damage to the skin,which leads to the infection of bacteria or drug-resistant bacteria,thus affecting the tumor treatment effect.In order to further overcome the interference of drug-resistant bacterial infection during tumor treatment,the construction and antibacterial mechanism of nano-antibacterial system were studied.We successfully developed a novel antibacterial nanosystem Dap@Au/Ag nanorods（Dap@Au/Ag NRs）based on gold nanorods,and used methicillin-resistant Staphylococcus aureus（MRSA）as the experimental strain to study Antibacterial properties of the new antibacterial agent.The results show that the novel antibacterial nanosystem Dap@Au/Ag NRs has remarkable bactericidal properties and can be used as a potential promising antibacterial drug,providing a new strategy for promoting and improving the effective antibacterial efficiency against drug-resistant bacterial infections.