Construction And Application Of Self-Assembled Nano Drug Delivery Systems Based On Floxuridine Prodrug

Chemotherapy is one of the most widely and effective methods to cure cancer.However,most of the chemotherapy drugs are poor solubility,low stability,rapid blood clearance and narrow therapeutic window,leading to the poor curative effect in the clinical treatment.With the thriving development of nanotechnology,the chemotherapy drugs have made great progress.Recently,prodrug-based self-assembed strategies have received the widespread attention in the drug delivery.The selfassembled nano drug delivery systems have many advantages,including simple in preparation,high drug loading capacity,good stability and controlled drug release.In this dissertation,focusing on developing new intelligent drug delivery systems,a series of controlled release self-assembled nano drug delivery systems have been developed by taking advantages of prodrug and self-assembed nanotechnology.Moreover,these systems have been investigated through in vitro for a variety of biomedical applications including drug delivery and cancer therapy.The detailed description is listed as follows:1.Prodrug-Based Self-Assembled Nanoparticles Formed by 3’,5’-Dioleoyl Floxuridine for Cancer ChemotherapyChemotherapy for cancer treatment is wildly used but remain restricted by several limitations,including inefficient drug delivery and concomitant adverse side effects.Herein,we reported a new prodrug-based self-assembled nanopartiele for the efficient treatment of cancer.Amphiphilic prodrug molecules(3’,5’-dioleoyl floxuridine,DOF)were constructed to form prodrug nanoparticles(DOF NPs)through a self-assembly process in water via hydrophobic interactions.The DOF NPs with high stability can be quickly enriched in tumor cells and release the floxuridine drug via hydrolysis of ester bonds by esterase.In vitro experiments reveal the DOF NPs possess satisfactory tumor killing effects and weak toxicity and side effects.These unique features could further promote the research progress of prodrug-based self-assembled strategies for the application of chemotherapy in cancer.2.pH-Responsive and Ce6-loading Self-Assembled Nanoparticles Formed by 3’,5’-Dioleoyl Floxuridine for Chemo-Photodynamic TherapyHigh-dose drugs often produce toxic side effects during chemotherapy,and single treatment methods are not effective.To address these problems,a pH-responsive selfassembled nano drug delivery system was developed for the combined chemophotodynamic therapy.Ce6 coated nano drug delivery system(Ce6@DOF NPs)was prepared by a one-step precipitation method,and the surface was modified with F-127,which improved the stability and biocompatibility.Ce6@DOF NPs are taken up by tumor cells,and release fluorouridine for chemotherapy and Ce6 for light-mediated photodynamic therapy in the lysosome.In vitro experiments show that Ce6@DOF NPs can effectively inhibit the proliferation of tumor cells under the light-mediated,and have good chemotherapy and photodynamic therapy capabilities.The self-assembled nano drug delivery system provides a new strategy for the combined chemotherapy and photodynamic therapy in clinic.