Synthesis Of Polymer Nanoparticles Functionalized Gold Nanomedicine Materials And Their Application In Tumor Diagnosis And Treatment

At present,cancer is a major factor affecting and endangering human life and health.Traditional treatment methods mainly include surgery,chemotherapy and radiotherapy,but these treatment methods have many shortcomings.For example,surgical treatment has certain limitations and the tumor is not easily removed.Chemotherapy and radiation therapy can cause damage to normal tissue cells.In recent years,with the development of nanotechnology,new therapeutic methods combining treatment and diagnosis can not only treat cancer,but also monitor the therapeutic effect in real time,thereby preventing the phenomenon of overdose or underdosing and reducing side effects.Gold nanomaterials have been widely used in the treatment and imaging of cancer due to their excellent optical properties,chemical inertness,shape control and easy functionalization,but they are very unstable and require modification of other ligands.The modification of gold nanomaterials by high molecular polymer not only improves the stability of gold nanomaterials,but also the composites have the advantages of combining polymers and gold.Therefore,in this project,we have functionalized gold nanoparticles through high molecular polymers for the integration of diagnosis and treatment of cancer.The specific research is as follows:1.Synthesis of gold nano-self-assemblies based on chitosan grafted poly(L-lysine)dendrimer and its diagnosis and treatment.Although gold nanomaterials have shown great potential in the treatment and imaging of cancer,the toxic reducing agents and templating agents are inevitably used in the synthesis of gold nanoparticles to reduce their biocompatibility.In order to solve this problem,first,We synthesized a novel chitosan-graft-poly(L-lysine)dendrimer(CPL)by click reaction using an azide-modified chitosan and a terminal alkynyl-containing PLLD and its use as a stabilizer,reducing agent and blocking agent to reduce chloroauric acid for self-assembly of Au NCs.This strategy does not use any toxic reducing agent during the synthesis process,providing a green synthesis method for the synthesis of Au NCs.Then,the Au@CPL NCs were modified with RGD to enhance their targeting.Finally,the gene pMMP-9 was treated with Au@CPL-RGD NCs.The physical and chemical properties were characterized by ~1H NMR,FT-IR,DLS,UV-VIS.The ability of Au@CPL-RGD NCs to bind pMMP-9 was detected by agarose electrophoresis technique and the particle size and potential of the complex were characterized by nano-laser particle size analyzer.Gene transfection experiments and Western blot experiments showed that Au@CPL-RGD NCs had better transfection efficiency than PEI25k;It was confirmed that Au@CPL-RGD NCs/pMMP-9 can effectively inhibit the proliferation and migration of MCF-7 cells by scratch and transwell experiments;Both in vitro and in vivo CT imaging have shown that Au@CPL NCs have potential for clinical use as CT contrast agents.finally,the therapeutic effect of Au@CPL-RGD NCs/pMMP-9 on tumors was studied by constructing a mouse tumor-bearing model,and the results showed that it has the best anti-tumor effect.2.Design and synthesis of gold nanorod-polydopamine nanostructures in the near-infrared II region and its tumor diagnosis and treatment research.At present,a single treatment method can no longer meet the needs of cancer treatment,and combination therapy has become one of the research hotspots.Based on the characteristics of gold nanoparticles that can convert absorbed light into heat,this chapter uses AuNR as a photothermal conversion agent and doxorubicin(DOX)chemotherapy to achieve a combination of photothermal and chemotherapy.The modification of AuNR by polydopamine not only improves the biocompatibility of AuNR,but also enables it to have photothermal properties in the near-infrared region(NIR-II region).Using AuNR@PDA as a vector,we constructed a targeted nano-diagnostic system with GSH-responsive release of DOX.The physicochemical properties were characterized by UV-VIS,FT-IR,transmission electron microscopy(TEM),mass spectrometry and thermogravimetry;photothermal performance test results show that Au NR@PDA-TAT-RGD has excellent photothermal performance;CT and PA imaging in vitro and in vivo indicates that Au NR@PDA-TAT-RGD has a promising future in clinical use as a CT contrast agent and a PA contrast agent;Cytotoxicity indicates that Au NR@PDA-TAT-RGD has good biocompatibility;In the tumor inhibition experiment,the combination therapy of Au NR@PDA@DOX-TAT-RGD showed better anti-tumor effect than photothermia or chemotherapy alone.