Construction And Drug Delivery Of ROS-responsive Poly(fluorene-phenylene Vinylene) Nanocarriers For Tumor And Inflammation Targeting

Using the drug delivery system(DDS)to deliver drugs can improve the distribution of the drug in the body,increase the dosage,reduce its toxic and side effects,and achieve the purpose of enhancing the therapeutic effect.In inflammation and cancer,the level of reactive oxygen species(ROS)will increase abnormally,so high ROS level is very suitable as a feature of disease.Polymer nanoparticles have simple preparation and separation,small transformation,high quantum measurement,and biological characteristics.Good compatibility,strong light stability,easy modification and other advantages have been widely used in the development.Conjugated polymer nanoparticles with vinylidene bonds react with ROS to be degraded and generate chemiluminescence.According to this principle,ROS stimulus-responsive copolymer nanoparticle drug delivery system can be synthesized.At the same time,the unique mechanism of chemiluminescence that does not require external light source excitation can further improve the visual stimulus-responsive conjugated polymer nanoparticle drug delivery system.A nano-drug delivery system responsive to ROS stimulation of the drug,and its drug release ability in inflammation and cancer has been studied.Therefore,the work of this paper is carried out through the following two aspects:1.Inflammation-targeted ROS stimuli-responsive conjugated polymer nanoparticlesIn this paper,the conjugated polymer(Poly[(9,9-di-(2-ethylhexyl)-9H-fluorene2,7-vinylene)-co-(1-methoxy-4-(2-ethylhex-yloxy)-2,5-phenylenevinylene)],PFV-coMEHPV)and amphiphilic copolymer PSMA as the main body to prepare conjugated polymer nanoparticles Dex-Celecoxib-CPNs.The nanoparticle is wrapped with an antiinflammatory drug celecoxib inside,and is externally modified with a targeting group targeting macrophages.Due to the abnormally high level of ROS in the inflammation site,the nanoparticles will be targeted to the inflammation site after intravenous injection into mice and will be oxidized and degraded by ROS to release antiinflammatory drugs to produce therapeutic effects.UV-Vis absorption spectroscopy and high performance liquid chromatography verified that the drug loading of the nanoparticles was 7.6%,and the encapsulated drug could be released within 15 minutes under the stimulation of hypochlorous acid.The chemiluminescence quantum yield(QY)of the nanoparticles was calculated to be 3.7 einsteins/mol by chemiluminescence analysis.Cell experiments proved that Dex-Celecoxib-CPNs has a good targeting ability to macrophages RAW264.7.Dex-Celecoxib-CPNs were dimensionally stable,have good biocompatibility,and have a high response to hypochlorous acid,and can be used for the treatment of arthritis model mice.After seven consecutive days of treatment,the administration of Dex-Celecoxib-CPNs reduced the swelling of the ankles of mice to 67%of the original,while the swelling of the ankles of the mice in the control group was 87%of the original It has a good effect on murine arthritis.2.Visualized stimuli-responsive conjugated polymer nanoparticles for tumor targeting Chemotherapy is still the main method of clinical cancer treatment,but most chemotherapeutic drugs have serious side effects.The use of drug delivery systems can improve the efficacy of chemotherapeutic drugs and reduce side effects.Most of the various types of drug delivery systems currently available cannot achieve visual monitoring of drug release.The realization of visual monitoring of drugs are very important for drug efficacy evaluation.Therefore,the design of a visual drug delivery system has important scientific significance and application potential.The skeleton of conjugated polymer nanoparticles can produce chemiluminescence and biodegradation after being oxidized.This unique mechanism enables real-time monitoring of the drug release process in vivo without the need for an external excitation light source,which overcomes the limited penetration depth of the fluorescent visualization drug delivery system,and is easy to Limitations such as photobleaching occur.In this thesis,conjugated polymer nanoparticles cRGD-5'-DFCR-CPNs were prepared by the nanoprecipitation method.The nanoparticle is wrapped with a chemotherapeutic drug inside,and the outside is modified with a tumor targeting group.UV-Vis absorption spectroscopy and high performance liquid chromatography verified that the drug loading of the nanoparticles was 13%,and the encapsulated drug could be released within 15 minutes under the stimulation of hypochlorous acid.The chemiluminescence quantum yield(QY)of the nanoparticles was calculated by chemiluminescence analysis method to be 3.45 einsteins/mol.C ell experiments proved that cRGD-5'-DFCR-CPNs can target human colon cancer cell HCT-116.cRGD-5'-DFCR-CPNs is dimensionally stable,has good biocompatibility,and has a high response to hypochlorous acid.It is preliminarily judged that it has the potential to realize the visualization of the drug release process.