Design, Construction And Biological Application Of LDHs-based Supramolecular Intercalation Materials

Supramolecular chemistry,dominated by non-covalent intermolecular forces,is developing rapidly in the cross fields of chemical biology,biophysics,and physical chemistry.Inspired by nature,supramolecular materials with different functions have been successfully developed through various non-covalent interactions.Layered double hydroxide（LDHs）is a kind of inorganic supramolecular host materials,which has unique 2D limiting effect,good biocompatibility and solid base properties.The immobilization of guest molecules by inorganic host matrix with good biocompatibility can not only protect intercalated molecules or cell therapy,but also increase their inherent properties（electrical,optical,magnetic,redox or acid-base properties）,thus forming new multi-functional biomaterials.Taking LDHs as the host,based on supramolecular intercalation assembly,SNP/MgMnFe-LDHs and DES-BPx/Mg Al-LDHs were constructed with sodium nitroprusside（SNP）and benzophenone derivative（BPx）respectively,and their unique properties and functions were explored.The potential applications in tumor therapy and cell imaging are explored according to their structure and properties.This paper provides an idea for the design,preparation,performance control and potential application of LDHs-based supramolecular intercalation materials.The main research contents are as follows:1.Inspired by natural enzymes,specific enzyme-like cascade catalytic reactions can be obtained by imitating the metal active sites of natural enzymes and assembling inorganic materials at the molecular level via supramolecular interaction,which can greatly expand their application in biology.Herein,it is reported that a bioinspired SNP/MgMnFe-LDHs（denoted as S2MFL）supramolecular nanoagent has been successfully synthesized via the intercalation between nitroprusside（SNP）with MgMnFe-LDHs.The resulting S2MFL is possessed of Peroxidase-,Catalase-and Oxidase（OXD）-like activities under tumor microenvironment（TME）stimulation.It should be noted that this S2MFL demonstrates a high OXD-like activity rate level of 9.508×10^-6 Ms^-1 in the chemodynamic therapy（CDT）study.Furthermore,the superoxide anions(O₂^·-)generated via OXD-like activity can react with NO（GSH-responsive）,followed by the production of reactive nitrogen species（RNS）.The synergistic reactive oxygen species（ROS）and RNS generation destroy intratumoral redox balance and extensively promotes cancer cell inhibition without additional energy introduction and has excellent T₁/T₂-weighted magnetic resonance imaging ability.Overall,this RNS-enhanced CDT strategy provides a novel approach for TME-mediated therapy.2.Based on the intercalation function and limiting effect of LDHs host,BP2,BP4,BP9 anions and decyl sulfonic acid anions（DES）were co-intercalated into the layers of Mg Al-LDH by a simple hydrothermal coprecipitation method to prepare DES-BPx/Mg Al LDHs（DBx MAL）.Surprisingly,under the excitation of 720-860 nm laser,DBx MAL can be excited by laser to emit green up-conversion fluorescence,and the emission wavelength is around the 520nm,which is consistent with the down-conversion emission wavelength.However,the up-conversion luminescence properties of BP derivatives were not found before intercalation.It can be inferred that the up-conversion luminescence properties may be caused by the LDHs-based intercalation system.The two-dimensional confinement effect and the confined microenvironment of LDHs induce the up-conversion of BPx anions.Through the study of its up-conversion luminescence phenomenon,the mechanism of two-photon absorption was determined.Good biocompatibility,suitable nanoscale and unique up-conversion luminescence ability allow us to explore its up-conversion confocal fluorescence imaging capability.It was found that He La cells incubated with DB₉MAL emitted green fluorescence under laser confocal microscope,and the cytoplasm was clearly visible.It can be speculated that it aggregates in the cytoplasm through endocytosis.In this work,the preparation of organic-inorganic supramolecular intercalation system based on LDHs provides a universal and simple way to improve and discover the new luminescent properties of existing guest molecules,which is helpful to expand its application field.