Controlled Preparation And Application Performance Of MOFs@ Natural Polymer As Novel Drug Carrier Based On Chemical Cross-linking Anchored

Natural polymers and other biomass resources have the advantages of environment-friendly,low price,renewable,high stability and good processability.However,due to its size,and distribution of the irregular pore,the drug loading of natural polymer carrier is low,and the release rate of drug is too fast in the early stage,which cannot meet the requirements of long-acting and sustained release.On the contrary,porous metal-organic frameworks（MOFs）with high and regular porosity have high drug loading and excellent properties of long-acting and sustained release.However,most of the MOFs are brittle and insoluble powders,which face great challenges during processing.Therefore,it is an urgent problem to develop new drug carriers with good processing performance and long-acting sustained-release properties.In this paper,based on chemical cross-linking anchored of MOFs with the active groups of natural polymers,a series of MOFs@natural polymers as novel drug carriers were prepared via in-situ growth.Herein,the chemical composition,crystal structure and surface morphology of MOFs@natural polymers were characterized by X-ray photoelectron spectroscopy,X-ray diffraction and scanning electron microscope.The relationships between the binding mechanism of MOFs and natural polymers and controllable preparation were studied.Furthermore,the application properties of drug loading,controllable drug release,antibacterial and others were systematically investigated,and the smart release mechanisms of the drug-loaded MOFs@natural polymers were also discussed.Moreover,the mathematical models of drug release were further established.Finally,the application effects of agriculture and food preservation were explored.Overall,this study aimed to provide new methods and new ideas for the development and utilization of MOFs@natural polymers as novel drug carriers.The main research contents and conclusions are as follows:（1）Based on chemical cross-linking of sulfonic acid groups on sodium lignosulfonate（SL）with protonated UIO-66-NH₂,the UIO-66-NH₂/SL as double-layer drug carrier was successfully prepared.And then it was used to the loading of thiamethoxam（TMX）.Besides the loading behavior of drug,the release behavior and mechanism of drug were also studied.Furthermore,the application performance of rice pest control was discussed.As a result,the payload of TMX in the UIO-66-NH₂/SL was up to 33.56±2.82%.And the time of TMX released from UIO-66-NH₂/SL was up to 1152 h in the soil,while that of uncoated TMX was only 144 h.TMX release was an abnormal release mechanism that was controlled by both Fickian diffusion and non-Fickian diffusion.Furthermore,a mathematical relationship of7)9)₄7))=1.0437)9)₄9)（9）+3.107 between TMX release from UIO-66-NH₂/SL in the soil and indoor was calculated by the release kinetics model,it could be used to predict and guide the rice pest control.In addition,TMX-loaded UIO-66-NH₂/SL had excellent stability and biological safety,in the greenhouse,none of the rice was affected by pests within 42 days,and the plant height of rice was up to 41 cm.In contrast,as for the control group of uncoated TMX,the rice was affected by pests at 16 days,and the plant height of rice was only 21 cm.The above results indicated that TMX-loaded UIO-66-NH₂/SL had a more efficient and sustainable control effect on rice pests compared to uncoated TMX.（2）Based on chemical cross-linking of the active groups（-COOH,-NH₂ and-OH）on carboxymethyl chitosan（CMCS）with Cu（II）ions,the ball-like,fiber-like and membrane-like HKUST-1@CMCS composites were controllably prepared by in-situ growth.As a result,the surface roughness（Rq）of matrix of the ball-like,fiber-like and membrane-like composites were 887,88.4 and 18.2nm,and the average sizes of HKUST-1 crystals on the corresponding composites were about 10.2,5.9 and 1.7μm respectively,implying that the size of HKUST-1could be controlled by tailoring the Rq of polymer matrix.The Rq of matrix was larger,the average size of HKUST-1 crystals was larger,and the drug loading of HKUST-1@CMCS composites was higher.Furthermore,the results of drug release showed that the release percentage of dimethyl fumarate from HKUST-1@CMCS was 66%in 326 h,while that of Cu@CMCS was only 12 h.Obviously,the HKUST-1@CMCS had long-acting and sustained release property compared to Cu@CMCS due to its complementary advantages of MOFs and polymers.（3）The above HKUST-1@CMCS was used as the carrier of the antibacterial agent.Then an eco-friendly,recyclable and intelligent food packaging was built,which was applied to antibacterial and strawberry preservation.As a result,the released amount of dimethyl fumarate with PBS stimulus was up to 75.4%at 84h,while that of released without stimulus was only 28.6%at that time,indicating that dimethyl fumarate-loaded HKUST-1@CMCS had intelligent release properties.Further mechanistic studies showed that the structure of HKUST-1@CMCS was destroyed step by step through different intensity of the stimulation of phosphate,thereby realizing intelligent release of antibacterial agent.With outstanding and long-acting antimicrobial activity,dimethyl fumarate-loaded HKUST-1@CMCS could effectively prolong the shelf life of strawberries as food packaging.In addition,HKUST-1@CMCS could easily regenerate,and regenerated HKSUT-1@CMCS still maintained intelligent response property.（4）Herein,flexible carboxymethylation modified filter paper（CMFP）was used as the substrate.Based on the chemical cross-linking of ordered carboxymethyl and hydroxyl groups on CMFP with nano MOFs,a new strategy for controllable,universal and large-scale preparation of materials was developed.The 6 types of nano MOFs@CMFP and large-scale MIL-101@CMFP were successfully prepared under mild conditions,which were applied to the applications of antibacterial and wound healing of pitaya stalk.As a result,the retention of ZIF-67 on the ZIF-67@CMFP was still up to 93.87%after the mechanical deformation and abrasion（200 cycles）,confirming that the nano MOFs@CMFP was flexibility and ultra-stability.Moreover,the crystal structure and compactness of MIL-101@CMFP composites with 70 times magnification had no obvious change compared with the sample before magnification,implying that this method not only had universal applicability,but also could be used for large-scale synthesis of flexible nano MOFs@CMFP.In addition,the results of cytotoxicity assay showed that the relative cell viabilities of nano MOFs@CMFP were higher than 80%,and the results of antibacterial test showed obvious inhibition zone on Escherichia coli and Staphylococcus aureus,indicating that nano MOFs@CMFP had the advantages of low toxicity and high antibacterial activity.Thus,the flexible nano MOFs@CMFP showed good effect of antiseptic and wound healing for the pitaya stalk.This study was expected to solve the problem of flexible use of nano MOFs in the practical application.（5）The above nano MOFs@CMFP was used as the carrier of curcumin（Cur）,and then a biological antiseptic patch with long-acting and intelligent release property was successfully prepared.Its drug release,antibacterial and antioxidant properties were studied,and it was applied to wound healing of pitaya stalks.As a result,the chemical stability of Cur-loaded nano MOFs@CMFP was significantly improved compared to uncoated Cur.The amount of Cur release from MIL-101@CMFP in PBS was only 24.2%at 360 h,while that of released with citric acid stimulus was up to 83.5%at that time;in addition,the inhibition zone diameters of Cur-loaded nano MOFs@CMFP on Staphylococcus aureus were greater than 9.6±1.0 mm,the antioxidant activities were higher than 87%at 2.0 mg?m L^-1 of Cur-loaded nano MOFs@CMFP.The above results implied that Cur-loaded nano MOFs@CMFP was a long-acting and intelligently drug release system,and had excellent antioxidant and antimicrobial activity.Therefore,Cur-loaded nano MOFs@CMFP had good effect of antiseptic and wound healing for the pitaya stalk.Compared with other fresh-keeping agents,this anti-decay paste was more convenient and efficient to use.In summary,this paper provides new ideas and technological methods for the universal,large-scale and controllable preparation of MOFs@natural polymers.These not only realize the high-value utilization of natural polymer,but also provide the basis and technical support for expanding the safe application of MOFs@natural polymers in the fields of agriculture and food preservation.