The Research On Nano-material Based On Covalent Organic Frameworks For Tumor Treatment Application

Until today,cancer still poses a serious threat to human life and health.Although there are currently a variety of clinical treatment methods,including surgical treatment,chemotherapy,radiotherapy,etc.,which have also achieved certain therapeutic effects.However,patients treated through these methods will also exposed to the disadvantages of high risk of recurrence and side effects on the human body.Conventional therapies can only provide patients with limited survival benefits and have a poor prognosis.Therefore,researchers have developed a variety of emerging cancer treatments to improve the treatment effect and minimize side effects.Covalent organic frameworks(COFs),as an emerging class of porous nanomaterial,have become a kind of biomedical nanomaterial with important application prospects due to its high porosity,high functionality and good biocompatibility.Although there have been some researches on the application of COFs in bioimaging,drug delivery and optical therapy,the exploration of COFs in biomedical applications is still relatively limited.In order to make better use of the advantages of COFs in the field of tumor treatment,we synthesized a series of COFs-based nanomaterials for effective tumor treatment and results monitoring in this article.The specific contents are as follows:(1)In Chapter 2,in view of the current difficulty in synthesizing COFs with a controllable nano-scale size(less than 200 nm)and uniform morphology,we used the core-mediated imine polymerization reaction to develope a nanomaterial,which was constructed by upconversion nanoparticles(UCNP)as the core,and porphyrin COFs as the shell,named UCCOFs.Using this strategy,we realized the controllable synthesis of COFs shells,and successfully obtained three kinds of UCCOFs with different shell thicknesses,including 35 nm,45 nm,and 60 nm.And they were confirmed to be able to effectively produce ¹O₂ through the internal energy transfer of nanoparticles under the excitation of NIR light,which can be used for PDT in vivo.(2)In Chapter 3,in response to the current problem that real-time monitoring cannot be achieved in the reactive oxygen species(ROS)mediated effective treatment of tumors,we based on the UCCOFs obtained in the previous chapter,by loading ¹O₂indicator ICG and PEGylation,prepared a self-reporting photodynamic therapy(PDT)nanomaterial called UCCOFs-1.Experiments have proved that UCCOFs-1 can effectively produce ¹O₂ to realize PDT under NIR laser irradiation.At the same time,the ICG loaded will be degraded by the ¹O₂ generated in the PDT process,and the fluorescence signal at 800 nm will turn on for real-time reporting the position and dose of the ¹O₂ in the body.In the mouse tumor experiments,by fitting the fluorescence signal intensity and the mouse tumor inhibition rate,it was found that there is a good linear relationship between them,which indicates that the luminescence intensity of UCCOFs-1 in vivo shows a good correlation with the therapeutic effect.The good correlation can be used to predict the treatment effect after treatment and adjust the treatment plan in time to achieve the best treatment.(3)In Chapter 4,in view of the low oxygen level in the tumor microenvironment,which leads to the low efficiency of PDT,we used porphyrin-based COFs to carry the chemotherapy drug doxorubicin(DOX)to form nanoparticle PCOFs-DOX to realize the combined treatment of phototherapy and chemotherapy at the tumor site.The nanoparticles can stably exist in the physiological environment.Due to the characteristics of porphyrin molecules,the particles can effectively produce ¹O₂ and photothermal effects under NIR laser irradiation.They can be used for combined treatment of PDT,PTT and chemotherapy,causing tumor cell damage and achieve high-efficiency treatment of tumor sites.