The Research On The Organic Targeted Fluorescent Nanometer Probe For Tumor Diagnosis And Therapy

Cancer,a malignant tumor,is one of diseases that threaten human health.Moreover,related studies have shown that the incidence and mortality of cancer have been increasing gradually.The common diagnostic methods are difficult to detect the occurrence of early tumors,because of poor sensitivity and specificity.Normally,most patients were detected tumors in the late stage and miss the best time to therapy.Therefore,it is urgent to develop new cancer diagnosis and therapy methods to achieve safe and effective tumor diagnosis and therapy.In recent years,the development of nanotechnology has provided new solutions for tumor diagnosis and treatment.Compared with traditional tumor contrast agents and drug delivery systems,nano agents have good biocompatibility and stability.Also,it can significan improve the accuracy and safety of tumor diagnosis and treatment.This paper combines nanotechnology and optical imaging technology to prepare a mitochondria-targeted DNA assembly drug delivery system(Cy5,5-DNA@DOX),and constructs nanoparticles that can target tumors through bioorthogonal reactions(DBCO-AIE-dots),and rubrene-bisoxalate nanoparticles that respond to the tumor microenvironment.The efifects of three kinds of nanoparticles on tumor diagnosis and treatment were evaluated.Including:Part ?:Mitochondrial targeting DNA assembled nano-drug delivery system(Cy5.5-DNA@DOX)for the application of tumor chemotherapy-sensitization.This system consists of three components:Cyanine dye Cy5.5,which not only acts as a mitochondrial targeting molecule but also produces reactive oxygen species(ROS),and increases the sensitivity of cancer cells to chemotherapeutic drugs;DNA fragments that form nano-trains by self-assembly as a biocompatible carrier;Doxorubicin(Dox),which as a therapeutic agent.The results show that Cy5.5 can produce a small amount of reactive oxygen species ROS under the laser irradiation of 660nm,which makes the cells in an oxidizing environment,and enhances the therapeutic effect of the chemotherapy drug DOX.Previous research has indicated that incubation of DOX with DNA results in the formation of a reversible physical conjugate,and intercalation of DOX within the DNA also quenchec DOX fluorescene.~When DOX released from the DNA the fluorescence can restore.Based on these principle,the release process of the drug in the cell can be monitored by the"on-off" of the fluorescence of DOX.Therefore,Cy5.5-DNA@DOX not only has the function of targeting tumor mitochondria but also can enhance the sensitivity of tumor cells to chemotherapeutic drugs.It is a versatile system for tumor diagnosis and therapy.Part ?:Aggregation-induced emission nanoparticles based on glucose metabolism engineering and in vivo click chemistry for txmor targeted diagnosis.The DBCO-AIE-dots was prepared by nano coprecipitation.We propose a two-step in vivo tumor-targeting strategy for AIE dots via metabolic glycoengineering and click chemistry,in the first step an azide group was expressed in tumor tissue by glucose metabolism engineering,and then attaching DBCO-AIE-dots specifically to the cell surface by a click reaction.The results show that the DBCO-AIE-dots can label fluorescent probes in tumor tissues by means of bioorthogonal metabolic labeling.The azide functional group at the tumor site can greatly enhance the enrichment of DBCO-AIE dots in tumors.Therefore,aggregation-induced emission nanoparticles based on glucose metabolism engineering and click chemistry have targeted effect,indicating that bioorthogonal reactions are a very powerful tool for tumor diagnosis,and with higher activity reactions are developed.Efficiency will be greatly improvedPart ?:H2O2-responsive chemiluminescent organic nanoprobes are used for the research of living tumor microenvironment.In this study,a nanoparticle Rb@CPPO containing bisoxalate(CPPO)and rubrene(Rb)was prepared.In the presence of excess H2O2 in the tumor microenvironment,Rb@CPPO can emit fluorescence without light.excitation.The results show that Rb@CPPO nanoparticles not only increase the stability of each molecule,but also increase the circulation time in the body.Moreover,Rb@CPPO nanoparticles can respond to excessive H2O2 in the tumor site,resulting in responsive chemiluminescence,enabling high specific imaging of tumors,improving the signal-to-noise ratio of tumor imaging,and avoiding autofluorescence of the organism interference.Therefore,Rb@CPPO chemiluminescent nanoprobes play an important role in the diagnosis and treatment of tumors.