| Cancer is currently one of the deadliest diseases in the world,and the threat and incidence of cancer to human health is still increasing due to the lack of effective treatment.Modern medicine has made great progress in the research of cancer treatment methods,the clinical use of cancer treatment means:surgery,chemotherapy,radiotherapy and phototherapy.However,due to the limitations of poor targeting,unsatisfactory therapeutic effect and poor prognosis,the clinical use of these methods is limited.With the rapid development of chemistry and biomedicine,the researchers found that the combination therapy had a better antitumor effect than monotherapy.However,due to the complexity of tumor microenvironment（TME）,combination therapy also has certain limitations,such as difficult precise positioning and controlled release of drugs,low bioavailability,and by-products,which seriously affect the therapeutic effect of combination therapy.The cascade reaction can effectively solve the above problems.The cascade chemical reaction has the characteristics of high efficiency,high bioavailability and few by-products.Combined with the characteristics of tumor microenvironment,the cascade reaction is introduced into combination therapy to trigger the cascade reaction under specific tumor conditions,realize the controlled release of the therapeutic agent at the tumor site,coordinate each treatment mode,magnify the effect and reduce by-products.It can effectively enhance the effect of combination therapy.In recent years,the rapid development of nanomaterials has brought new ideas for improving the disadvantages of tumor therapy.Nanomaterials have good physical and chemical properties,which can be used as delivery agents of anticancer drugs,as well as kill cancer cells through energy conversion,such as light and ultrasonic.In addition,nanomaterials have advantages in enhancing penetration and retention effect（EPR）passive targeting of tumors,effectively accumulating at tumor sites,reducing drug side effects,improving bioavailability,and improving therapeutic efficiency.Nowadays,More and more biomedical nanomaterials are widely used in the field of tumor therapy.As an important new nanomaterial,porous framework materials have been widely concerned in the field of cancer therapy due to their customizable structure,adjustable surface properties and high porosity.Metal-organic frameworks（MOFs）have the advantages of structural diversity,high porosity,large specific surface area,and easy functionalization.MOFs multifunctional nanomaterials with customizable structures have great potential in cancer therapy such as chemotherapy,phototherapy,immunotherapy,and combination therapy.Covalent organic frameworks（COFs）have the advantages of low density,excellent biocompatibility,high chemical stability,customizable porosity and ordered topological morphology.They have the advantages of tumor site targeting,therapeutic agent responsive release,and low systemic toxicity in tumor therapy.Therefore,based on the excellent performance of porous framework materials and the excellent performance of the cascade reaction in tumor combined therapy,this thesis designed and synthesized a nano-cascade platform based on metal-organic framework and covalent organic framework for cancer therapy.The main contents are as follows:In the first part,an acid-responsive cascade nano platform was designed and synthesized based on metal-organic framework materials for tumor starvation/gas/photothermal therapy.MPDA as a nanocarrier,then loaded Mn CO and GOx@ZIF-8（Mn CO@MPDA@GOx-ZIF-8）.Mn CO@MPDA@GOx-ZIF-8 NCs accumulate effectively in tumor sites through EPR effect,degradation of ZIF-8 shell sensitive to acidic tumor microenvironment,exposure of GOx,GOx catalyzes endogenous glucose to gluconic acid and H2O2,and promotes the reaction of Mn CO with H2O2 to produce cytotoxic gas CO.In addition,the decomposition of glucose also cuts off the energy supply chain of tumor cells.As a photothermal agent,MPDA can cause thermal damage to tumor cells and promote the generation of CO under near infrared light irradiation.The enzyme-catalyzed cascade activated by the acidic tumor microenvironment promotes the production of toxic CO and combined with photothermal therapy can effectively ablate the tumor.Based on the excellent performance of the MOF-based cascade system in tumor combination therapy in the first part,the covalent organic framework without metal and with excellent biocompatibility was selected in the second part,and the cascaded nanoplatform based on the covalent organic framework materials was constructed for tumor catalytic/photothermal/photodynamic combination therapy.2,2’-azo-bis（3-ethylbenzothiazolin-6-sulfonic acid）（ABTS）was supported by iron-porphyrinyl COFs（Fe-TphDha）as the carrier.The oxidation of ABTS into ox ABTS with strong near-infrared light absorption was promoted by the inherent peroxidase activity of Fe-TphDha nanase.In addition,ox ABTS consume glutathione（GSH）in situ,thereby enhancing catalytic therapy and PDT,and demonstrating excellent antitumor efficacy at both cellular and in vivo levels. |
