Application Of Composite Nanoparticles To Enhance Chemodynamic Therapy

Nowadays,the number of deaths due to malignant tumors in the world is increasing every year,and the treatment of malignant tumors is still a major problem that plagues relevant scholars.Although the traditional treatment has achieved some success,it has been difficult to meet people’s needs due to its many shortcomings and the dramatic growth of cancer types and the number of patients.Researchers have proposed chemodynamic therapy（CDT）,which has been proved to be effective in inducing cell death and has excellent tumor treatment effects.Recently,more and more researchers have designed a variety of composite nanotherapeutic systems based on CDT.Combination therapy,which combines two or more treatments with CDT,is gradually replacing single CDT therapy.The combination of CDT therapy can reduce the toxic side effects of chemotherapy drugs and overcome the H in the tumor cell microenvironment H₂O₂Compared with single treatment,Synergistic treatment of multiple treatment methods can inhibit tumor cell tissues more efficiently.In order to further improve the effect of tumor treatment,the traditional chemotherapy drugs have poor targeting,poor solubility and other problems,we designed and synthesized CDT/PTT and CDT/CT combined therapy nano platform for tumor treatment research,the specific content is as follows:In the first chapter,we briefly introduce the traditional treatment methods of cancer,and then introduce the new treatment methods in detail.We focus on the development and application of CDT based combination therapy nano platform.In Chapter 2,we briefly introduce the experimental drugs,experimental,testing and characterization methods,cell culture and animal model establishment.In Chapter 3,a CDT/PTT nanoplatform based on polydopamine（PDA）was prepared.PDA nanoparticles were first prepared by solution oxidation,and then Fe and epigallocatechin-3-gallate（EGCG）were used³⁺The coordination action forms a layer of metal polyphenol network on the surface of PDA,and EGCG@PDA is successfully prepared.EGCG@PDA has good biocompatibility and small particle size,which can be enriched in tumor tissue by EPR effect.EGCG,PDA and Fe were released by EGCG@PDA decomposition in the tumor microenvironment³⁺.PDA,as a typical photothermal agent,can increase the temperature of tumor cells to induce cell death under light irradiation.EGCG can inhibit heat shock proteins to improve the therapeutic effect of PTT,and at the same time,it can promote Fe³⁺More importantly,the increase of cell temperature will further promote the Fenton reaction and further enhance the effect of CDT.In Chapter 4,we prepared a metal-organic framework MIL-101（Fe）-based nanoplatform loaded with the chemotherapeutic drug dihydroartemisinin（DHA）for combination therapy of CDT and CT.Dihydroartemisinin（DHA）was encapsulated in the pores of metal-organic framework MIL-101（Fe）,and the drug was blocked using cyclodextrin（OTs-β-CD）.After that,polyethylene glycol（PEG）was used to coat the surface of the material,and finally the final carrier（DHA@MIL-CD-PEG NPs）was obtained.The negative charge on the surface of the final carrier can effectively avoid phagocytosis by normal cell tissues,and it can be enriched in the tumor area by EPR effect.In the tumor microenvironment,the nanoplatform was cleaved and the drugs DHA and Fe were released³⁺.On the one hand,the released Fe³⁺The Fenton reaction can occur in tumor cells to produce CDT effect,on the other hand,DHA can be Fe³⁺CDT catalyzes the production of carbon free radicals,induces cell apoptosis,and further improves the therapeutic effect through the synergy of CDT and CT.In summary,we successfully synthesized polydopamine nanoparticles coated with metallic polyphenol networks,and the experimental data in vitro and in vivo showed that the synthesized nanoparticles had excellent therapeutic effects.At the same time,a chemical drug delivery nanocarrier loaded with dihydroartemisinin with metal-organic framework was designed,which combined chemotherapeutic therapy with chemotherapeutic therapy.In vitro experiments proved that the designed and synthesized nanoparticles had obvious toxic effect on tumor cells.