Construction Of Iron-based Metal-organic Framework Composites And Their Application In Reactive Oxygen Species Regulation

Cancer is a major problem that plagues human health.Traditional treatment methods,including surgical treatment,chemotherapy,and radiotherapy,have disadvantages such as large trauma and weak targeting.The exploration of accurate,efficient and minimally invasive treatment has become the research focus of current tumor therapy.Reactive oxygen species are substances with redox reaction activity in cells.Excessive reactive oxygen species can effectively promote cancer cell apoptosis under the action of carcinogens.Accurate and effective cancer treatment can be achieved by controlling the in situ generation of reactive oxygen species in tumor cells.Chemodynamic therapy and photodynamic therapy are two effective treatment methods for in-situ reactive oxygen species production in tumor cells,with high therapeutic efficiency and small negative effects,which overcome the shortcomings of traditional treatment.Therefore,the establishment of a collaborative treatment platform based on reactive oxygen species generation of chemodynamic therapy and photodynamic therapy is a key breakthrough in cancer treatment.However,oxygen-dependent photodynamic therapy is li mited by the low concentration of oxygen in tumor cells.Chemodynamic therapy relies on the Fenton reaction catalyzed by Fe²⁺,which is limited by the decrease in Fe²⁺content during the Fenton reaction.How to overcome the deficiency of oxygen and Fe²⁺at the same time is the key to improve the efficacy of chemodynamic therapy and photodynamic therapy combined therapy.Metal-Organic Framework is composed of metal ions or metal ions clusters and multi-dentate organic ligands through coordination.The functi on of metal-organic framework can be flexibly adjusted by changing the structural units.By constructing an iron-based metal-organic framework with irons as a metal nodes and porphyrin as building unit,and adjusting the content of Fe²⁺and Fe³⁺by introducing reductants,Fe²⁺can be provided for chemodynamic therapy and oxygen can be provided for photodynamic therapy.Fe²⁺and Fe³⁺generate hydroxyl radicals and oxygen through Fenton reaction and Fenton-like reaction with excess hydrogen peroxide in tumor cells,respectively,which can greatly improve the combined therapeutic effect of chemodynamic therapy and photodynamic therapy.Here,we designed multifunctional composite nanomaterials based on porphyrinated iron-based metal-organic framework nanoparticles,and applied them to tumor therapy.The main contents are as follows:(1)We synthesized a new porphyrinated iron-based metal-organic framework with iron metal center and porphyrin as secondary building units through a simple solvothermal method,and then a film was formed by Fe³⁺ion and tannic acid onto the metal-organic framework to design and synthesize iron-based metal-organic framework loaded with Fe³⁺and tannic acid.The formed composite degrades in an acidic environment and gradually releases Fe³⁺.Then tannic acid acts as a strong reducing agent to reduce most of Fe³⁺to Fe²⁺,making the solution system show a small amount of Fe³⁺coexist with a large amount of Fe²⁺.Fe²⁺and Fe³⁺catalyze hydrogen peroxide to produce hydroxyl and oxygen,respectively.Under light activation,oxygen is further converted into singlet oxygen m ediated by photosensitizers.(2)In order to improve the lack of Fe²⁺supply during chemodynamic therapy and insufficient oxygen supply during photodynamic therapy,we use the composite for the combined therapy of chemodynamic therapy and photodynamic therapy to achieve the regulation of active oxygen in tumor cells.In the absence of light,it is proved that the composite material can increase the supply of Fe²⁺and promote the effect of chemical kinetic treatment.Based on the expression of intracellular hypoxia protein,the oxygen supply effect of the composite material in photodynamic therapy was explored.It is found that a large amount of active oxygen can be produced und er light excitation,and a good therapeutic effect can be obtained.