Construction Of MOF-808-DTPA-Gd Magnetic Resonance Contrast Agent And Its Application In Mediating Photothermal Therapy

With the progress and development of society,people's living standards have improved significantly,but the accompanying diseases have also begun to appear,of which cancer is a major threat to human health.To overcome the threat of cancer,researchers in various countries around the world are working to develop more precise and minimally invasive diagnostic methods to fight cancer.Among them,molecular imaging techniques such as magnetic resonance imaging,ultrasound imaging,and computed tomography are the main means of cancer detection.Among these imaging technologies,magnetic resonance imaging?MRI?has the advantages of high penetration depth,accurate soft tissue contrast,and no radiation,and is widely used in clinical diagnosis.In order to optimize MRI sensitivity,provide higher sensitivity and signal-to-noise ratio,and obtain higher resolution images,contrast agents are usually required in clinical diagnosis to enhance the contrast between the lesion tissue and normal tissue,especially for some serious diseases?such as Early tumors?.Therefore,the development of contrast agents with high relaxation rates is particularly important.In addition,multifunctional nanoparticles with combined diagnostic and therapeutic functions show great promise in personalized nanomedicine.The development of integrated reagents with both diagnostic and therapeutic functions is not only beneficial to the early diagnosis of certain diseases,but also has important clinical significance for the treatment of lesions found in time.Based on this,this paper takes the metal-organic framework?MOF-808?nanoparticles with porous structure as the platform,and mainly performs the following work:The first part is the study of constructing Gd-based T1 magnetic resonance contrast agent based on MOF-808.We modified the Gd chelate?Gd-DTPA?into the pores of the porous metal organic framework?MOF-808?using a geometrically restricted strategy to construct a Gd-based magnetic resonance contrast agent with high relaxation rate.Firstly,MOF-808nanoparticles were prepared by hydrothermal method;then DTPA was connected to the Zr₆ cluster in the channel of MOF-808 to modify DTPA in the channel;finally,DTPA was chelated with Gd to prepare a highly dispersible MOF-808-DTPA-Gd nanoparticles.The solution experiment results show that MOF-808-DTPA-Gd has excellent T₁imaging effect,and its r₁ relaxation rate reaches 35.6 mM^-1s^-1?0.5 T?,which is 7.7times that of the commercial Gd-DTPA contrast agent.In vivo MRI imaging results show that the mouse bladder area has a very good T₁ imaging effect,but the tumor site T₁ imaging effect is poor.It may be that the MOF-808-DTPA-Gd molecules enter the mouse body from the MOF-808 channel falling off causes the material to be quickly metabolized.The second part is the construction of MOF-808-DTPA-Gd@polyaniline therapeutic integrated reagent and its application in MRI-mediated photothermal therapyBased on the first part of the work,we modified polyaniline?PANI?on the surface of MOF-808-DTPA-Gd nanoparticles.On the one hand,polyaniline can restrict the DTPA-Gd molecules from falling out of the MOF-808 channel;on the other hand,polyaniline is a good photothermal material,can be used for photothermal treatment.The results of the solution experiments show that the nanoparticles after polyaniline modification still maintain a high relaxation rate,r₁ is 30.1 mM^-1s^-1?0.5 T?,and has a good photothermal effect.After intratumoral injection of materials in mice,the T₁signal at the tumor site was increased by a factor of 3.3,which was 1.3 times that of the equivalent measurement of DTPA-Gd signal injection.Moreover,the MRI results of mice also showed better T₁ imaging effects and Longer imaging time,where the signal at the tumor site reached a maximum after 8 hours of injection?signal increased by a factor of 2.4?.In addition,8 hours after tail vein administration,the tumor site of the mice was irradiated with near-infrared light at 808 nm.The tumor growth of the mice was significantly suppressed,and the major organs of the mice were not significantly damaged after the treatment,indicating that MOF-808-DTPA-Gd@polyaniline is a good photothermal therapeutic agent.This work may provide some inspiration for using MOF materials to build a high-performance integrated platform for magnetic resonance contrast agents and treatments.