Design,Preparation And Imaging Research Based On Covalent Organic Framework And Its Derivatives

Cancer,also known as malignant tumor,is a disease in which certain normal cells are transformed by endogenous or exogenous carcinogenic factors to form abnormal cells with biological features such as abnormal divergence and proliferation,infiltration and metastasis,which then develop into tumor tissue.Due to the abnormal proliferation of tumor cells and their ability to invade normal tissues and even metastasize throughout the body via the lymphatic system and blood circulation,cancer is often difficult to cure and is a serious and lethal disease.Early detection and diagnosis of cancer is the key to cancer treatment.If cancer is detected and diagnosed correctly and treated effectively,the cure rate and survival rate of cancer can be greatly improved.As a result,there is a great deal of interest in how cancer can be more accurately and promptly diagnosed and treated.Tumor markers provide very effective and essential information for the diagnosis,prediction and treatment of tumors.Nucleic acid probes are fragments of known nucleic acid sequences with markers that hybridize with their complementary nucleic acid sequences,forming a double strand,and so can be used for the detection of specific gene sequences in the nucleic acid sample to be tested.Since the recognition between the two single strands is achieved by base complementary pairing,the method is extremely specific.With the continuous progress of nanotechnology,nanomaterials have become a hot topic of interest for researchers.Therefore,combining nucleic acid probes with nanomaterials to prepare functional nucleic acid nanoprobes for cancer imaging is a popular research topic.With the benefits of high sensitivity,rapid response,stability and simplicity,functional nucleic acid nanoprobes have been widely used in biomedical and other fields.Covalent organic frameworks(COFs)are a class of organic porous polymers with periodic and crystalline structured units linked by covalent bonds to form periodically porous crystalline covalent organic framework materials.The high crystallinity,stability,versatility and good biocompatibility of COFs are advantages that make them show great potential in the field of biosensing and imaging.Based on covalent organic frameworks(COFs)and their derivatives as nanomaterials,we designed and build two functional nucleic acid nanoprobes for the ultra highly sensitive detection of m RNA in the tumor cells,and this thesis focuses on the following two aspects:1.A fluorescent nanoprobe(Tp Dh-DT)enabling cancer biomarker TK1 m RNA-specific imaging and target-triggered drug release was designed and synthesized based on COF.Porphyrin COF nanoparticles(NPs)were used as carriers of adriamycin(Dox)and Cy5-labeled single-stranded DNA(ss DNA)was used for TK1 m RNA recognition.The COF NPs burst the fluorescence of Cy5 by fluorescence resonance energy transfer and achieve fluorescence recovery in the presence of a specific TK1 m RNA target.Loading Dox within the pores of COF NPs enhances the interaction between COF and ss DNA,effectively increasing the loading density and fluorescence burst efficiency of ss DNA,thus effectively preventing drug leakage.As a result,the nanosystem exhibited low fluorescence signal and reduced toxicity in normal cells.In cancer cells,the over-expressed TK1 m RNA and acidic microenvironment can emit strong fluorescence signal and induce drug release.This nanosystem provides new insights into the design of COF nucleic acid nanosystems in the field of analysis and cancer therapy.2.Two carbonized nanoprobes(C-COF-survivin and C-COF-TK1)were designed and synthesized based on carbonized COF(C-COF)for tumor cell imaging.COF NPs with highly crystalline structure were prepared at room temperature,and further prepared by pyrolysis of COF under inert atmosphere.The graphene-like mesoporous carbon structure of C-COF gives it enhanced UV-Vis absorption effect,photothermal conversion ability and solution stability.Compared with COF NPs,the porous C-COF NPs have better nucleic acid loading ability and fluorophore bursting effect,and the prepared nanoprobes have lower background fluorescence.In the presence of a target,the dye-labeled recognition sequence is readily released to "turn on" the fluorescence signal.With excellent specificity,good stability and high biocompatibility,the nanoprobe is a useful tool for intracellular TK1 and survivin m RNA imaging.