Mn-porphyrin Metal-organic Framework Is Used In MRI-mediated Self-supplying Photodynamic Therapy Research

In recent years,with the increasing environmental pollution and food safety problems,cancer has become the most serious disease endangering human health.In terms of treatment,traditional treatment methods such as surgery,radiotherapy and chemotherapy have long treatment cycles,large side effects and great pain to patients.Therefore,more gentle and safe treatment methods have attracted more and more attention.Photodynamic therapy?PDT?has received wide attention for its non-invasiveness and unique selectivity.As an important method for treating tumors,it mainly stimulates photosensitizers to undergo electronic transitions through light,and then transfers energy to oxygen molecules to produce cytotoxic reactive oxygen species?such as ¹O₂?and kill tumor cells to achieve the purpose of treating tumors.However,in the process of photodynamic therapy,hypoxia in the tumor microenvironment severely limits the production of reactive oxygen species,which greatly affects the effectiveness of photodynamic therapy.In terms of diagnosis,magnetic resonance imaging?MRI?has the advantages of non-ionizing radiation,high spatial resolution,and multi-dimensional imaging.It is an important imaging technology for clinical diagnosis.However,the currently used small-molecule Gd-based contrast agents have problems such as poor imaging results and potential biological toxicity.Manganese-based magnetic resonance contrast agents have received widespread attention due to their potential to replace Gd-based contrast agents,but manganese-complexes often exhibit low T₁-relaxation rates.Based on this,we constructed a porous metal-organic framework?PCN-222?Mn??using Mn-porphyrin ligands and six-core Zr₆ clusters.Because the Mn metal sites with catalytic function and affecting water proton relaxation are densely distributed in the open channels with hydrophilic properties,PCN-222?Mn?exhibits a very high r₁ relaxation rate and excellent catalytic hydrogen peroxide production of oxygen performance.Using hydrogen peroxide overexpressed in the tumor microenvironment,PCN-222 can overcome tumor hypoxia and improve the effect of photodynamic therapy.The main work of this article is as follows:First,PCN-222?Mn?nanoparticles with a particle size of about 150 nm were synthesized by solvothermal method using zirconyl chloride and Mn-porphyrin ligands as raw materials.XRD,infrared and ultraviolet absorption spectra were used to characterize the structure of the synthesized material.PCN-222?Mn?nanoparticles have good stability in aqueous solution,Tri buffer solution and medium.Next,the in vitro solution magnetic resonance imaging of PCN-222?Mn?was investigated to catalyze O₂ production and photodynamic properties of H₂O₂.Experimental results show that PCN-222?Mn?has excellent T₁-weighted imaging performance,and its r₁relaxation rate reaches 30.3 mM^-1s^-1?0.5 T?,which is 6.5 times that of the commercial contrast agent Gd-DTPA(r₁=4.6 mM^-1s^-1).In addition,PCN-222?Mn?has good performance in catalyzing the decomposition of H₂O₂ to produce O₂ in both neutral and slightly acidic?pH=7.4 and 6.5?.At the same time,under hypoxia conditions with H₂O₂,PCN-222?Mn?can convert O₂ produced by catalytic H₂O₂ decomposition to ¹O₂ after 660 nm laser light irradiation.Next,a series of cell therapy experiments were performed to verify the photodynamic therapy effect of PCN-222?Mn?.First,the cytotoxicity of the material was evaluated by MTT experiments.The results showed that PCN-222?Mn?had good biocompatibility.Then,different treatment groups were set up,and the effects of PCN-222?Mn?cell photodynamic therapy under normoxic and hypoxic conditions were characterized by MTT experiments,laser confocal imaging and flow cytometry.The results showed that the cell survival rates of the PCN-222?Mn?+H₂O₂ group were22%and 30%,under the conditions of normoxic and hypoxic after 8 min of 660 nm laser irradiation,which were far lower than those of the other treatment groups.These results indicate that in the presence of H₂O₂,PCN-222?Mn?can catalyze the O₂produced by the decomposition of H₂O₂ to improve the photodynamic therapy effect under hypoxic conditions.Finally,the effects of magnetic resonance imaging and photodynamic therapy of PCN-222?Mn?were verified by in vivo experiments on mice.After tail vein administration,magnetic resonance T₁ imaging results showed that the liver,kidney and tumor sites of the mice gradually became brighter over time;the brightest signals point of tumor,kidney and liver sites were 8 h,8 h and 4 h after injection;the strongest signals increased by 65%,90%and 83%,indicating that PCN-222?Mn?has good T₁-weighted imaging performance.According to the information of magnetic resonance imaging,after administering a 660 nm laser irradiation to the tumor site of the mouse for 8 min after tail vein injection,the tumor growth of the PCN-222?Mn?treatment group was significantly suppressed,and crusted after a period of time falling off;while the tumors in the other treatment groups did not significant change after light exposure,indicating that PCN-222?Mn?can use the tumor microenvironment overexpression of H₂O₂?catalyzing its decomposition to produce O₂ for photodynamic therapy?to enhance the therapeutic effect.We further confirmed the effect of photodynamic therapy through mouse organ sections,and there was no major damage to the main organs of the mice after treatment.This study may provide a reference for the construction of simple new integrated diagnostic and therapeutic reagents.