Study On Theranostical Application Of Two Dimensional Palladium-Based Nanomaterials In Different Animal Models And Embryotoxicity

In recent years,with the rapid development of nanotechnology,it has played an increasingly important role in energy,catalysis,industrial production and life sciences.Especially in biomedicine,the research on theranostic platforms based on nanomaterials has been springing up,because of their incomparable unique advantages.Owing to the passive targeting ability of nanomaterials,the biological imaging,drug delivery and the multi-model diagnosis and treatment can be realized,which is expected to open a new access to the treatment of cancer and to provide new ideas.The safety of nanomaterial is also the key element of the clinical transformation of nanomaterial from "paper" to "life".This paper is based on the two-dimensional(2D)palladium-based nanomaterial,aims to make breakthrough in animal models and proves that there is tumor targeting ability on the bigger animal models,which will make contributes to the clinical application of 2D Pd-based nanomaterials.And we expanded the scope of application by surface modification and loading to design a novel theranostic agent.In the last part,we explored the biosecurity of SPNS by its embryo safety.The contents of each chapter are as follows:Chapter 1:This chapter mainly summarizes the situation of theranostic applications of nanomaterials and where thereare going.We introduced the applications of nanomaterials on the different animal models and clinical medicine,meanwhile include the advances in the embryo safety research.Finally we explained the gist and significance of the topic.Chapter 2:In this chapter,we have synthesized two-dimensional(2D)Pd-based nanomaterials include the small Pd nanosheets(SPNS)and Pd@Au nanosheets(Pd@Au NSs)which have been surface-modified and functionalized with SH-PEG and Cy5.5.SPNS and Pd@Au NSs had favorable EPR effects on the rabbits and rats by in vivo fluorescence imaging and biodistribution experiments.Through the results of blood circulation and urine excretion,it was proved that the biobehavior on the bigger animal models still depended on the size of nanomaterial.The blood biochemical analysis and histologic section experiments indicated the safety of materials in vivo.Finally,we utilized the photothermal therapy to realize the treatment of tumor owing to the excellent absorption in the NIR region of SPNS and Pd@Au.To sum up,the 2D Pd-based nanomaterial is an ideal tumor theranostic nanoplatform on bigger animal models.Chapter 3:Considering that the prominent progress achieved in the research of hypoxia microenviroment in tumor,we successfully synthesized the Pd@Au@MnO2 nanomaterial based on the Pd@Au NSs which has excellent tumor targeting ability.This novel theranostic nanoplatform not only kept the remarkable absorption in NIR rigion but also could generate O2 by decomposing the H2O2 to enhance the effect of chemotherapy.After modification by HSA,DOX could be loaded effectively on the surface of nanomaterial,and the release of DOX was regulated by the pH and glutathione(GSH).In the last we confirmed the photothermal and chemical combined therapy completely eliminated the tumors in vivo.Chapter 4:The safety of nanomaterial is a great concern for many scientists.In this chapter,we choose the embryos of mice as the research object to systematically discuss the embryo toxicity of 5nm Pd NSs(SPNS).Firstly,we proved that the SPNS had favorable safety on the mouse embryonic fibroblast(MEF)in the level of cells.Preliminarily,we found that the SPNS could across the placental barrier to enter the 2nd-generation mice if we double the dose of injection.Meanwhile the SPNS won't affect the normal growth of the pregnant or 2rd-generation mice and the SPNS mainly existed in the placent by biodistribution experiment.Chapter 5:We summarized the study of this dissertation and made a prospect for the future research work.