Design,Synthesis And In Vitro Photodynamic Properties Of Metal-Organic Frameworks Loaded With Photosensitizers

As the second leading cause of death worldwide,cancer is depriving millions of people of their lives every year.At this stage,traditional clinical cancer treatment is mainly performed by surgical resection,chemotherapy,radiation therapy,etc.However,these traditional treatments are not only costly,require repeated administration,have low treatment efficiency.but also have many side effects such as vomiting and hair loss,which will weaken the patient's willingness to survive.Therefore,we urgently need to study more effective and less side-effect treatments to bring hope to patients.Photodynamic therapy,as one of the emerging cancer treatment methods,is a specific response to the diseased site,which is less cytotoxic to normal cells,and the laser is directly irradiated to the diseased site,which causes less damage to the patient's skin and also reduces the pain of repeated administration in traditional therapies.At present,the main problems encountered in photodynamic therapy are the easy aggregation of photosensitizers,insufficient depth of light penetration,and low treatment efficiency.In addition,because the microenvironment of the tumor is mainly hypoxia and the overall acid reduction environment,which is detrimental to the photodynamic response that requires oxygen.At the same time,glutathione in the reduction environment will consume active oxygen and weaken the photodynamic effect.Metal-Organic frameworks are hybrid porous crystalline material,which have excellent designability and biocompatibility,and their specific pores can be used for loading drugs or photosensitizers.When applied to photodynamics,MOFs can make photosensitizers amphiphilic,allowing a sufficient amount of photosensitizers to enter the lesion site.We can also design MOFs according to the tumor microenvironment to solve the problems of hypoxia and reactive oxygen quenching encountered in photodynamics.Aiming at the problem that photosensitizers are easy to aggregate and quench,PHF@ZIF-8 was designed and synthesized in this paper.Fullerene C₆₀ with photodynamic properties was modified to polyhydroxy fullerene by phase transfer oxidation method,and PHF@ZIF-8 was synthesized by one-pot method.PHF@ZIF-8solves the problem of poor solubility and easy aggregation of C₆₀,it can also generate reactive oxygen superoxide anion that kills cancer cells under 448 nm laser irradiation.At the same time,PHF@ZIF-8 is amphiphilic and can be more efficiently reach the lesion sites and can be better dispersed in tumor tissue.This shows that PHF@ZIF-8has better photodynamic performance than the application of C₆₀.Aiming at the problem that tumor hypoxia microenvironment hinders photodynamic development,Fe³⁺@UiO-66-NH-Ce6 was designed and synthesized in this paper.The combination of MOFs and the photosensitizer Ce6 facilitates the diffusion of active oxygen and prevents the aggregation and quenching of active oxygen.The loaded Fe³⁺reacts with excess H₂O₂ in cancer cells to generate oxygen,which changes the hypoxic microenvironment of the tumor and promotes the effectiveness of photodynamic.This indicates that Fe³⁺@UiO-66-NH-Ce6 is expected to be used in clinical cancer treatment.Aiming at the problem of glutathione consumption of reactive oxygen species in tumor microenvironment,a new crystal ZJU-922 with one-dimensional channels was designed and synthesized in this paper.ZJU-922,synthesized from Zn²⁺and disulfide ligands,can consume glutathione,which promotes photodynamic progress.Zn²⁺released by the decomposition of MOFs has the effect of killing cancer cells,and during the reaction,the delivery process of Ce6@ZJU-922 can be monitored by detecting the fluorescent signal.This indicates that Ce6@ZJU-922 has the ability to consume glutathione to promote photodynamic performance and can kill cancer cells with Zn²⁺.It also has the effect of fluorescence monitoring,which is expected to be used in clinical treatment.