Construction And Application Research Of Composite MOF Fluorescent Probe For Double Detection Of Bioactive Molecules

Biologically active molecules such as phosphate,GSH,H⁺,etc.play an important role in maintaining the normal physiological activities of the human body.The normal level and activity of these small biological molecules not only helps to maintain the health and balance of the biological environment,but also can reliably indicate abnormalities and diseases when the content of these small molecules is deviated.Therefore,monitoring multiple bioactive molecules simultaneously and studying the dynamic changes and molecular interactions of these biomolecules deeply are of great significance for assessing the occurrence and development of diseases,studying disease's development mechanisms,and developing new drugs.In addition,fluorescence imaging technology has unique advantages in detecting active molecules distributed in time and space,and has become an indispensable and effective tool for monitoring active molecules in living systems.Based on this,this paper designed and synthesized two types of core-shell structure composite metal-organic framework fluorescence sensors for two diseases,namely liver injury induced by hyperthyroidism and diabetic ketoacidosis,by cleverly combining nano-fluorescent materials and molecular biology technology.Through the simultaneous detection of phosphate/GSH and phosphate/p H respectively,this paper deeply studies the close relationship between hyperthyroidism-induced liver damage and phosphate/GSH,as well as the close relationship between diabetic ketoacidosis and phosphate/p H,which can provide a useful tool for the early diagnosis of liver damage caused by hyperthyroidism and diabetic ketoacidosis.The specific content is as follows:1.Hyperthyroidism-induced liver injury is quite common in clinic.Therefore,developing rapid and simple methods for the assessment of hyperthyroid liver injury is of great significance.Considering phosphorus metabolism is disordered because of hyperthyroidism,and the hyperthyroid liver injury is closely related to the abnormal level of glutathione(GSH).Thus,development of a new method that can simultaneously detect changes in blood phosphorus and GSH levels of serum,liver,kidney and other organs to assess the degree of hyperthyroid liver injury is necessary for clinical medical research.Herein,a new core-shell structured composite metal-organic frameworks(MOFs)nanoprobe(Ui O-66(OH)₂@Cu-MOFs)was designed and synthesized,which showed excellent performance in the fluorescence detection of phosphate and GSH.Ui O-66(OH)₂ as the core,its metal node Zr(IV)realizes the specific detection of phosphate,and Cu-MOFs as the shell,the active site Cu(II)of porphyrin center realizes the specific detection of GSH.Finally,the nanosensor was applied for evaluating different degrees of hyperthyroid liver injury in mice models by monitoring serum,liver,kidney and other organs'blood phosphorus and GSH levels based on fluorescence detection and two-photon in situ fluorescence imaging.And found that the levels of phosphate and GSH in serum were negatively correlated with the degree of hyperthyroid liver injury,while the changes of phosphate and GSH levels in the liver and kidney organs were positively correlated with the degree of hyperthyroid liver injury.In general,the present works provide a new way to effectively evaluate liver injury induced by hyperthyroidism in the early clinical stage.2.Diabetic ketoacidosis is one of the most common acute complications of diabetic patients.Therefore,developing a method that can quickly and conveniently assess diabetic ketoacidosis is of great significance.Due to a severe lack of insulin in the body,metabolic acidosis and lower blood p H are caused.At the same time,lower blood phosphorus is a secondary result of diabetic ketoacidosis,making blood phosphorus levels closely related to diabetic ketoacidosis.Therefore,it is necessary to develop a multifunctional probe that can simultaneously detect p H and phosphate in serum and kidneys to assess diabetic ketoacidosis for clinical medical research.Based on this,we designed and synthesized the nanosensor Al-MOF@PCN-224,which can simultaneously detect phosphate and p H.Al-MOF as the core,the protonation of the amino group on the organic ligand realizes the detection of H⁺,and PCN-224 as the shell,its metal node Zr(IV)realizes the detection of phosphate.Finally,the nanosensor was applied to a mouse model of induced type 1diabetes to realize the fluorescence detection of phosphate and p H levels in the mouse serum,and the two-photon in situ imaging of phosphate and p H in the kidney organs.We found that the p H and phosphate level in the serum of diabetic mice were lower than the normal level,while the p H in the kidney was lower than the normal level and the phosphate was higher than the normal level.In general,the present works provide a fluorescent tool for the early diagnosis of diabetic complications-ketoacidosis.