Research On Cooperative Diagnosis And Treatment Of Tumor Based On Hollow Mesoporous MnO₂ Nanospheres

Combined cancer therapy has been proven to be more effective in inhibiting cancer.It can not only solve the shortcomings of monotherapy,but also play a mutually reinforcing role between the various therapies,thereby enhancing the anti-cancer effect.In this work,we synthesized hollow mesoporous MnO₂ nanospheres（H-M-pp）and used them as carriers to complete drug loading,in vivo transportation,and targeted drug delivery,so as to achieve a strategy of combining multiple therapies to treat cancer.In this paper,the second chapter to H-M-pp as the carrier,at the same time of improving tumor lack oxygen environment combined with Photodynamic Therapy（Photodynamic Therapy,PDT）,chemical Therapy（Chemotherapy）,Gene Therapy,Gene Therapy and Immunotherapy（Immunotherapy）"five effects in one"combination Therapy in non-small Cell Lung Cancer（Non-Small Cell Lung Cancer,NSCLC）.First,the photosensitizer Ce6 and the chemical drug DOX were loaded,and the drug was passed through the mesopores on the surface of the manganese dioxide into the hollow cavity using the principle of high concentration soaking.Next,EDC and NHS were used to activate three kinds of oligonucleotide chains modified with5’-NH₂ group,and amide reaction was used to connect with manganese dioxide nanospheres with-COOH group on the surface to synthesize H-M-pp/C&D+3 Nanoparticles.The three oligonucleotide chains are:Aptamer-S6,an aptamer that targets A549 cells;miR-145,a single-stranded RNA that inhibits the migration and invasion of A549 cells;and the oligodeoxidized nucleotides of CPG motif that activate immune cells.Similarly,the attachment of oligonucleotide sequences to the surface of manganese dioxide nanoparticles can also improve their stability in organisms.The manganese dioxide nano-platform that targets A549 cells for fluorescence calibration of tumors and comprehensive treatment of"five effects in one"realizes a coordinated therapeutic mechanism of integrated diagnosis and treatment.Because photodynamic therapy uses an external laser light source,it is limited to have a good therapeutic effect on local superficial tumors.Therefore,how to apply photodynamic therapy to deep tumors and exert their excellent therapeutic effects requires further research and development.In previous research reports,the use of chemiluminescent substances to provide chemical energy to activate photosensitizers so as to avoid the need for laser irradiation is an effective measure to solve this problem.In the third chapter,the hollow mesoporous MnO₂nanosphere is used as the carrier to construct a novel treatment strategy to initiate a cascade of biological orthogonal reactions.The hollow cavity of MnO₂ nanospheres was loaded with CPPO and the photosensitizer Ce6,and H-M-pp/C&C+GOx nanoparticles were formed by the combination of amide reaction and Glucose Oxidase（GOx）.After entering tumor cells,GOx on the surface of the nanoparticle consumes glucose in the cell to produce H₂O₂ and provide positive guidance for the reactive cleavage of the manganese dioxide nanoshell.At the same time,the manganese dioxide nanoshell breaks down to release the loaded drug and generate oxygen to enhance photodynamic therapy.The effect of CPPO and H₂O₂ produces chemical energy to activate Ce6 to convert O₂ to ROS and cause toxicity to cells.Among them,O₂ and H₂O₂ needed for photodynamic therapy and starvation therapy can be generated in situ circulation,without relying on the carrying of drug loaded nanoparticles,and each reaction plays a positive role in promoting,so as to play the best therapeutic effect.