Synthesis Of Al/Eu-hemorphyrin Metal-organic Frameworks For Photodynamic-sonodynamic Therapy Of Tumors

Cancer threatens human life,health and quality of life seriously.In order to treat cancer,researchers have developed a large number of new technologies.Among them,photodynamic therapy(PDT)and sonodynamic therapy(SDT)have attracted great attention.The mechanism of these two diagnosis and treatment technologies is as follows:the sensitizer is injected into the tumor site,and after laser or ultrasound(US)irradiation,the internal tumor sensitizers produce reactive oxygen species(ROS,such as ~1O₂),which induce cell death.The key to realize the combination of PDT/SDT is the development of sensitizers that can respond to light and US.Traditional sensitizers mainly include inorganic semiconductor nanoparticles(such as Ti O_2-x),organic molecules(such as porphyrin molecules and phthalocyanine molecules)and Metal-organic framework(MOF).MOF have many advantages such as adjustable composition,pore structure,easy surface modification,and degradability,which have attracted widespread attention in recent years.However,most MOFs used for cancer treatment still have the following problems:(1)The function of MOFs is single,which limits the therapeutic effects of these MOFs;(2)Diagnosis and treatment performance needs to be improved;because conventional MOF uses heavy metal ions as nodes,energy transfer is prone to occur,resulting in MOF fluorescence quenching and ROS yield reduction.Therefore,the MOF composed of heavy metal ions will have severe fluorescence quenching,which will reduce the yield of ROS and affect the effect of tumor treatment.In order to solve the above problems,this paper uses hematoporphyrin monomethyl ether(HMME)as the organic ligand,and uses the rare earth element Eu and the light metal element Al as the metal nodes to construct two new types of MOF.These two materials are used as sensitizers for tumor PDT-SDT combined therapy,and have achieved good tumor treatment effects.The main results of this paper are as follows:(1)Synthesis,performance characterization and photo-sono dynamic combined therapy of Eu-hemoporphyrin metal-organic framework materials(Eu-MOFs).Europium(Eu)element is a typical lanthanide rare earth luminescent element.In this chapter,Europium chloride and HMME are dissolved in a mixed solvent of ethanol and N,N-dimethylformamide(DMF),and Eu-MOFs are obtained after hydrothermal reaction at 120? for20 hours.Eu-MOFs use Eu and HMME as metal nodes and organic ligands,respectively,and self-assemble to form nanoparticles with a particle size of about 180 nm.After surface modification with phospholipids(DSPE-PEG),Eu-MOFs-PEG nanomaterials exhibit excellent hydrophilicity and can be well dispersed in water and biomass solutions.Under the action of light(660 nm,100 m W cm^-2)or US(1 MHz,1.75 W cm^-2),Eu-MOFs-PEG nanomaterials can produce ~1O₂.In vitro cell experiments show that Eu-MOFs-PEG nanomaterials have good biocompatibility and can significantly increase the ROS level of CT26 cells under US or light excitation.In addition,PDT-SDT combination therapy can kill cancer cells more efficiently,and the therapeutic effect is significantly better than that of PDT or SDT alone,which proves the high efficiency of the combination therapy.Therefore,Eu-MOFs nanomaterials are expected to become a new type of photo-sono sensitizers and used in PDT-SDT combined therapy of cancer cells.(2)Synthesis and performance characterization of Al-hemoporphyrin metal-organic framework materials(AlHFs)and the study of combined photo-sonodynamic therapy for tumors.Most of the MOF materials currently used for cancer treatment are composed of heavy metal ions(such as Fe³⁺,Cu²⁺)as nodes.However,due to the paramagnetic and unsaturated 3d orbitals of heavy metal ions,their fluorescence and photoacoustic sensitization effects will be severely quenched,which will affect the therapeutic effect of PDT or SDT.In order to solve these problems,we synthesized AlHFs with Al³⁺ions as the metal node.The material is formed by self-assembly of Al³⁺and HMME,with a particle size of about 185 nm.AlHFs-PEG was obtained after surface modification with DSPE-PEG.Comparing AlHFs-PEG with the MOF material composed of heavy metal elements Feand HMME(FeHFs-PEG).It is concluded that under the excitation of 660 nm light,the ~1O₂ yield of AlHFs-PEG is 3.6 times that of FeHFs-PEG.Under the excitation of US,The ~1O₂ yield of AlHFs-PEG is 2.8 times that of FeHFs-PEG.AlHFs-PEG has high biocompatibility.They can be absorbed by cells and produce ~1O₂ to effectively destroy cancer cells.It has high biosafety and photoacoustic sensitization.The growth rate of tumors injected with AlHFs-PEG was significantly inhibited under the combined action of light and US,showing a better therapeutic effect than PDT or SDT alone.