MOF Enhances The Release Of Reactive Oxygen Species And Evaluation Of Anti-cancer Performance

In modern society,the incidence and mortality of cancer are increasing constantly.Social surveys have found that,almost every family has a family member who died of cancer in China.In the treatment of cancer,chemotherapy and radiotherapy are the most common treatments.Chemotherapy can inhibit tumor growth effectively through chemical drugs.However,because chemotherapy is administered systemically and the drugs are not recognizable,chemotherapy has considerable toxic side effects and can cause irreparable damage to vital organs throughout the body.In addition,chemotherapy also has complex drug resistance,which can develop resistance to multiple drugs.Therefore,the top priority now is to develop targeted anti-cancer drugs to reduce side effects.Nanomaterials have the advantages of small size,large relative surface area,and good biocompatibility,so they can be used as carriers to load chemotherapeutic drugs.In addition to the advantages of nanomaterials such as large specific surface area,MOF in nanomaterials also has the advantage of adjustable pore size.By using the many advantages of MOF,cancer treatment and detection can be combined,chemotherapy and other therapies can be combined.In the second chapter,the solvent method was used to synthesize MIL100(Fe)at room temperature,and MIL100(Fe)with different Fe(Ⅱ)content was obtained through different reaction times.Because MIL100(Fe)has Fe(Ⅲ)/Fe(Ⅱ)with redox characteristics,the release of Chemotherapy drugs Doxorubicin hydrochloride(DOX)is not only controlled by p H,but also related to the concentration of GSH,so that the release of DOX is more accurate.Among them,Fe(Ⅱ)can react with intracellular H2O2 through Fenton reaction to generate Hydroxyl radicals(·OH).Fe(Ⅲ)consumes glutathione(GSH)and produces O2,which leads to changes in the tumor microenvironment.As an active substance that can reduce reactive oxygen species(ROS),consuming GSH increases the amount of ROS.The hypoxic environment of cancer will promote the proliferation and metastasis of cancer cells.Fe(Ⅲ)/Fe(Ⅱ)in the above two reactions can be transformed into each other in the process of mutual conversion reaction,the problem of hypoxia and reducing substances is solved at the same time.The cytotoxicity and biocompatibility of the DOX@PEG-MIL100 nano-drugs were evaluated in KOPN8 cancer cells and U937 cancer cells,indicating that the nanoparticles themselves do not damage cells,but they have a very powerful anti-cancer function after loading DOX.In Chapter 3,firstly,Hf-TCPP NMOFs(70 nm)were synthesized using the traditional solvent method,and single-atom Pt(Hf-TCPP@Pt)was loaded on the surface.Because TCPP is a photosensitizer,Hf-TCPP has a good photodynamic therapy effect.However,the therapeutic effect of photodynamic therapy is greatly affected by the hypoxic environment in cancer cells,and Pt can react with H2O2 to produce O2,thereby solving the problem of hypoxia in cancer cells.Then,ultra-small Hf-TCPP QDs(2 nm)were synthesized by the same method.Compared with Hf-TCPP NMOFs,Hf-TCPP QDs can generate more ROS under the same reaction conditions.Although quantum dots are easy to diffuse in cells,they cannot use the EPR effect to accumulate near cancer tissues.Therefore,Hf-TCPP QDs and DOX are wrapped with lipids to form larger DOX@Hf-TCPP@LIPs(30 nm)to achieve light The purpose of combining dynamic therapy with chemotherapy.In short,DOX@Hf-TCPP@LIPs can accumulate to the vicinity of cancer tissues through EPR,while Hf-TCPP QDs are smaller in size and can spread better in cancer cells,thereby achieving the purpose of targeting cancer cells.