Stimuli-Responsive Porphyrinic Reticular Materials For Photo/Chemo Dynamic Therapy

Porphyrin is a highly conjugated macrocyclic structure that consists essentially of four pyrrole rings,and thus has excellent chemical and thermal stability and unique photophysical and electrochemical properties.However,the inherent shortcomings such as instability and self-quenching under physiological conditions,limit their biomedical applications.In recent years,reticular materials(MOF or COF)have become research hotspots due to their adjustable size,designable structure and function.The reticular materials can assemble the nanoparticles or biomolecules into a single framework to achieve multiple functions.Therefore,it is widely used in various fields,especially in life science,which has huge potential.In this thesis,we innovatively designed and synthesized the responsive porphyrinic reticular materials,which can not only take advantages of the photophysical and chemical properties of porphyrin,but also modulate the relationship between structure and function to achieve the synergistic effect.In first work,a parallel lipid peroxide accumulation strategy was designed based on catalytic metal-organic frameworks(MOFs)for enhanced ferrotherapy.The bimetallic MOF was synthesized with iron porphyrin as a linker and cupric ion as a metal node,and erastin,a ferroptosis inducer,was sandwiched between MOF layers with4,4’-dipyridyl disulphide as spacers.Under tumor microenvironment,erastin was released from the layered MOFs via a glutathione-responsive cleavage.The exfoliated MOFs served as a dual Fenton reaction inducer to generate numerous hydroxyl radicals for the accumulation of lipid peroxide while erastin aggravated glutathione depletion to down-regulate glutathione peroxidase 4,which then inhibited the consumption of lipid peroxide.Therefore,a parallel lipid peroxide accumulation strategy was established for enhanced ferrotherapy which effectively inhibited tumor growth in living mice,opening up new opportunities to treat apoptosis-insensitive tumors.In the second work,we have synthesized the covalent organic framework(COF)with 5,10,15,20-tetrakis(4-aminophenyl)porphyrin and light control ligand(1,2-bis(5-formyl-2-methylthiophene-3-yl)cyclopentene,which responds to light stimulation.Under the irradiation of ultraviolet light,a closed ring will be formed between two thiophenes.Through the light response of the light-controlled ligand,the COF switch is realized,which can regulate the effect of COF photosensitivity to produce singlet oxygen.And we have further studied its light stimulation regulation mechanism,which provides the fundamentals for the subsequent development of stimuli-responsive photosensitizers.