Study On Mimic Enzyme Activity Of Two-Dimensional Pd-Based Nanomaterials And The Related Nano Diagnosis And Treatment Systems

In recent years,with the rapid development of nanotechnology,nanomaterials,has been widely used in many areas of human activities due to their unique size-dependent,physical and chemical properties.Eespecially the application of nanomaterials in biomedical field has attracted great interests.It has become a research hot spot to design and synthesize new-type nanomaterials with uniform size,shape,composition and specific surface functional groups and to study their applications in biological fields such as bioanalysis,biological imaging and cancer diagnosis and treatment.However,how to fabricate simple nanomaterials with unique biological characteristics to achieve good bioanalysis or theranostic effect are still important challenges in nano-biotechnology.Based on this,a series of palladium-based nanomaterials were designed and prepared by controlled synthesis technique.Then their mimic enzyme activities were investigated and the catalase activity was applied to improve the hypoxic tumor microenvironment.A new therapeutic agent based on palladium-based nanomaterials was prepared.Considering the metal nanomaterials can not be degraded in vivo as well as in order to optimize the design of complex nanomaterials in combination therapy,we have prepared a single laser-irradiated nano diagnosis and treatment system integrating photothermal thermodynamics therapy,which is applied to imaging guidance cancer treatment.The details of each chapter are as follows:Chapter 1:A brief summary of some biological applications of nanomaterials,which focuses on the two studies of mimic enzyme and cancer diagnosis and treatment.First of all,the research progress,enzyme activity and related applications of several kinds of nanoenzyme were summarized;Secondly,the research progress and applications of nano-materials in cancer diagnosis and treatment,especially in photothermal and photodynamic therapy,were introduced.Finally,the significance and research contents of this thesis were described.Chapter 2:In the second chapter,we investigated the mimetic enzyme activity of two-dimensional?2D?Pd-based nanostructures?e.g.Pd nanosheets,Pd@Au and Pd@Pt nanoplates?and found they possessed intrinsic peroxidase-,oxidase-and catalase-like activity,catalyzing hydrogen peroxide or dissolved oxygen to oxidize organic substrate and decomposition of hydrogen peroxide to generate oxygen.Then the peroxidase-like activity of these Pd-based nanomaterials with different structures and compositions was investigated systematically,and the results indicated that their catalytic activities were structure-and composition-dependent.Among them,Pd@Pt nanoplates displayed the highest peroxidase-like activity.Based on these findings,Pd-based nanostructures were applied to the colorimetric detection of H₂O₂ and glucose,or electro-catalytic reduction of H₂O₂.Chapter 3:Based on the study of the catalase activity of Pd@Pt nanomaterials in Chapter 2,in this chapter,Pd@Pt-PEG-Ce6 therapeutic reagent was designed and synthesized by covalently linking the photosensitizer Ce6 with Pd@Pt-PEG-NH₂..The prepared Pd@Pt-PEG-Ce6 nanocomposite can decompose endogenous H₂O₂ of cells or tumors to produce oxygen,achieving the effects of regulating the hypoxia trumor microenvironment and enhancing the photodynamic therapy.In vitro and in vivo experimental results clearly indicated that compared with free Ce6,the photodynamic therapy based on Pd@Pt-PEG-Ce6 exhibited higher cancer treatmnet outcomes.Chapter 4:In order to reduce the complexity of nano reagent synthesis and treatment process in the photothermal and photodynamic combined treatment,in this chapter,a novel theranostic nanoplatform?SiNcOH-DSPE-PEG?NH₂?NPs?has been successfully developed by coating silicon 2,3-naphthalocyanine dihydroxide?SiNcOH?with DSPE-PEG and DSPE-PEG-NH₂ for photoacoustic?PA?imaging-guided PTT and PDT tumor ablation for the first time.The as-prepared single-agent SiNcOH-DSPE-PEG?NH₂?NPs not only have good water solubility and biocompatibility,but also exhibit high photothermal conversion efficiency and singlet oxygen generation capability upon 808 nm NIR laser irradiation.In addition,owing to their high absorption at NIR region,the SiNcOH-DSPE-PEG?NH₂?NPs can also be employed as an effective diagnostic nanoagent for photoacoustic?PA?imaging.In vitro and in vivo experimental results clearly indicated that the simultaneous and combined PTT and PDT under the guidance of PA imaging with single NIR laser excitation can effectively kill cancer cells or eradicate tumor tissues.Taking facile synthesis and high efficiency in cancer treatment by SiNcOH,DSPE-PEG?NH₂?NPs into consideration,our study provides a promising strategy to realize molecular imaging-guided combination therapy.Chapter 5:Summarize the research work of this paper and make a prospect for the follow-up research work.