Design And Synthesis Of Iron-based MOF Nanocomposites And Their Applications In Cancer Therapy

Cancer has become a major chronic disease that threatens human health.How to effectively treat cancer is also a big problem in the medical field.Traditional cancer treatment methods include surgery,chemotherapy,radiotherapy and so on,but these traditional treatment methods still have shortcomings such as inadequate treatment efficiency and large side effects.Therefore,some new cancer treatment methods are beginning to emerge,which is expected to overcome the shortcomings of traditional cancer treatment.At present,the new treatment methods include chemodynamic therapy,photodynamic therapy,ferroptosis therapy,starvation therapy,etc.The new treatment methods have been widely developed because of the advantages of high efficiency and low side effects.However,the efficiency of a single treatment is still limited.It is still very important to improve the effect of cancer treatment to achieve the synergistic therapy of multiple treatment methods on a single material.Metal organic framework materials?MOF?have approved to possess great potential in the field of biomedicine because of their large specific surface area,controllable structure,high loading efficiency and no long-term toxicity.More importantly,the unique design of MOF makes it possible to integrate multiple therapeutic functions into the same nano-synergistic therapeutic system at the same time.Compared with other MOFs,iron-based MOF constructed with iron as a metal node have more prominent advantages in the application of cancer treatment.Firstly,as an essential element of life,iron has no biological toxicity.Secondly,some new cancer therapies,such as artemisinin-mediated chemodynamic therapy and ferroptosis therapy,need the participation of iron.The use of iron-based MOF can solve the problem of endogenous iron deficiency in these therapies.In this paper,two kinds of iron-based MOF nanocomposites were designed and synthesized based on iron-based MOF,calcium carbonate,dihydroartemisinin,glucose oxidase,cell membrane and so on.Specifically,it includes the following two aspects:1.A programmed release platform of dihydroartemisinin?DHA?to synergistically treat cancer with CaCO₃ mineralized metal-organic framework?MOF?was designed to treat cancer.Firstly,a porphyrin-based nanoscale MOF Fe-TCPP?NMOF?was synthesized to load DHA and further mineralized by CaCO₃ on the surface to encapsulate DHA?NMOF@DHA@CaCO₃?,which could significantly avoid the DHA leakage during transportation in bloodstream.When NMOF@DHA@CaCO₃ reached the tumor sites,the weak acidic microenvironment dissolved outer CaCO₃ layer to generate NMOF@DHA and Ca²⁺.Then NMOF@DHA was internalized by tumor cells,the high concentration of GSH reduced Fe³⁺of NMOF to Fe²⁺,leading to the collapse of NMOF structure.Along with the structure collapse,DHA was finally released and TCPP was activated,enabling the synergistic Fe²⁺-DHA mediated chemodynamic therapy,Ca²⁺-DHA mediated oncosis therapy,and TCPP mediated photodynamic therapy.In vitro and in vivo experiments demonstrated that the nanoplatform showed negligible toxicity to normal tissues with specifically programmed release of DHA and the anticancer efficiency was enormously enhanced by adopting triple synergistic therapy method.The platform could provide more opportunities for the design of safe,controllable,and effective drug delivery platforms.2.A cascade bioreactor was designed and developed for tumor-targeted starvation therapy and ferroptosis therapy.Iron-based MIL-100 nano metal-organic framework?MOF?was first prepared as a source of exogenous iron and used as a carrier for glucose oxidase?GOx?.The GOx-loaded MIL-100 was then further coated with a cancer cell membrane to obtain MIL-100@GOx@C.Due to the camouflage function and homologous targeting ability of the cell membrane,MIL-100@GOx@C can be preferentially taken up by cancer cells.Subsequently,a cascade reaction occurs in the cells.GOx catalyzes the production of gluconic acid and H₂O₂ by glucose.The higher concentration of GSH in the cancer cells reduces Fe³⁺in MIL-100 to Fe²⁺.Subsequently,Fe²⁺reacts with H₂O₂ to produce ROS,which induces ferroptosis in cells.