Design And Synthesis Of Oxygen-doped Black Phosphorus Nanoparticles And Its Application And Mechanism In Photothermal Triggered Immunotherapy Of Tumors

Since the 21 century,the incidence and mortality of malignant tumors have been high.And rising year by year,becoming a well-deserved number one killer.As the pathogenesis and cause of tumor is more complex,and the development mechanism of its internal environment has not been understood.Therefore,the traditional treatment can not effectively treat the progress of malignant tumors.At present,the common clinical treatment methods include: internal and surgical resection,chemotherapeutic drug therapy,traditional radiation therapy and so on.Unfortunately,these methods have great limitations.For example,surgical treatment is often unable to remove it completely,and it is very easy to relapse.Radiotherapy and chemotherapy has great harmful effect,has toxic side effects on normal cells and has strong drug dependence.Therefore,the development of safe and effective treatment strategies has an inestimable clinical demand.Therefore,there are many new treatments,such as gene therapy,immunotherapy,photothermal photodynamic therapy and so on.At present,photothermal therapy is a new method for the treatment of cancer.To put it simply,photothermal treatment of(PTT)is through a nanomaterial(with high photothermal conversion efficiency),which is injected into the body,and then irradiated directly with a near-infrared light source,which can convert light energy into thermal energy,which will cause the temperature of the place irradiated by the laser to rise and kill tumor cells.PTT treatment has three main advantages: first,from the patient's point of view,it can reduce the pain of patients;second,laser irradiation time is short,usually a few minutes to complete;third,photothermal materials are generally non-toxic and harmless,and have less toxic and side effects on the human body.Good photothermal conversion material is the premise of good or bad photothermal treatment effect,generally need to have the following advantages:first: have a strong photothermal conversion efficiency,which is essential;second: the material should be non-toxic or has a very slight low toxicity,this kind of material is used in organisms,once it produces toxicity,it will directly threaten human life.Based on this,in this paper,we designed and synthesized three kinds of photothermal materials based on phosphorus,and doped black phosphorus with three oxygen elements(sulfur,selenium,tellurium)to stabilize black phosphorus.At the same time,we also explored the anti-tumor activity of three elements doped black phosphorus in vivo and in vitro.1.Design and Synthesis of O-doped Black phosphorus Nanofilms and study on the Mechanism of stabilizing Black phosphorusIn this chapter,oxygen-doped black phosphorus nanowires(S@BPNSs,Se@BPNSs,Te@BPNSs)were synthesized by vapor deposition method using red phosphorus and sulfur powder,selenium powder and tellurium powder as raw materials and tin iodide and tin as catalysts.These three oxygen elements and oxygen elements all have more empty orbitals,which can accommodate the excess lone pair electrons on the surface of black phosphorus.We complement the advantages of these three oxygen elements and black phosphorus,hoping to effectively capture the lone pair electrons on the surface of black phosphorus,stabilize black phosphorus and make it a long-term photosensitizer.More importantly,we have studied the bonding of oxygen group elements and black phosphorus,and we are surprised to find that it may be the reason for the formation of heterojunctions.The experimental results show that,compared with the single black phosphorus system,the oxygen group element doped black phosphorus nanosheets have better stability and long-term photothermal properties.2.Design and synthesis of selenium-doped black phosphorus nanotablets and their photothermal therapy in tumorsIn this chapter,we use the material "selenium doped black phosphorus(Se@BPNSs)" synthesized in the second chapter as the follow-up biological experimental material.On the one hand,because selenium is one of the essential trace elements in human body,it has more empty orbitals which can effectively capture the lone pair electrons on the surface of black phosphorus.At the same time,we found that Se@BPNSs has better blood compatibility and lower hemolysis rate than BPNSs,S@BPNSs and Te@BPNSs.On the other hand,a large number of literatures in our research group have reported that selenium has excellent anti-tumor activity and good biocompatibility.Based on this,we choose Se@BPNSs as our follow-up experimental material.We know that black phosphorus has good photothermal conversion efficiency and can be used for photothermal anti-tumor.In addition,some studies have found that thermal ablation of tumors can stimulate a strong anti-tumor immune response and activate the body's immune response,while the immune escape of tumors makes it difficult for tumors to be treated effectively,mainly because of the expression of PD-1 and PD-L1 signal pathways.Therefore,we need to combine immunocheckpoint inhibitors and combine tumor photothermal therapy with immune checkpoint blocking therapy in order to bring a new concept of tumor therapy.In summary,we designed and synthesized three kinds of photothermal materials:sulfur-doped black phosphorus(S@BPNSs),selenium-doped black phosphorus(Se@BPNSs)and tellurium-doped black phosphorus(Te@BPNSs).With black phosphorus as the main body,it is doped with oxygen group elements Se and Te to capture the lone pair electrons on the surface of black phosphorus to stabilize black phosphorus.At the same time,the anti-tumor activity in vivo and in vitro was evaluated and analyzed.