Preparation And Performance Of Stimuli-Responsive Covalent Organic Frameworks Based Nanoparticles Drug Delivery System

Covalent organic frameworks(COFs)are a class of newly emerged crystalline porous polymers linked by dynamic covalent bonds.Due to its unique and attractive features,it has been greatly developed in recent years in various fields such as gas storage,photovoltaic materials,heterogeneous catalysis and drug delivery.In this thesis,three stimuli responsive COFs were designed and synthesized by changing the building blocks,and the preparation and performance of stimuli responsive covalent organic frameworks-based nanoparticles drug delivery system were also explored.We obtained three stimuli responsive COFs by solvothermal synthesis,these COFs were linked by imine or hydrazone and gained the unique redox sensitivity by introducing disulfide bonds in the building blocks.We performed a series of characterizations of three COFs,such as FT-IR,PXRD,TGA and so on.The results showed that the three COFs have high specific surface area,uniform porosity and excellent thermal stability,as the strong stability of imine or hydrazone itself,the three COFs can withstand a variety of solvents,but in an acidic environment,the imine or hydrazone were broken and the skeleton structure of the COFs were destroyed.We explored the potential of stimuli responsive COFs-based nanoparticle drug delivery systems for drug delivery.In order to improve the poor water dispersibility of COFs,three drug delivery systems,DOX-BTA-DITH-COF@P188,DOX-BTADIAM-COF@P188 and DOX-BTA-DDBA-COF@P188,were prepared by solvent replacement with poloxamer 188.Compared with the other two drug delivery systems,DOX-BTA-DITH-COF@P188 was stable under physiological conditions(p H=7.4),and can respond quickly to environmental stimuli.In-vitro cytotoxicity and cell uptake experiments showed that DOX-BTA-DITH-COF@P188 has strong cytotoxicity and good endocytic properties,a large amount of DOX was found in both cytoplasm and nucleus.These results indicated that DOX-BTA-DITH-COF@P188 with p H-redox dual sensitivity has great potential in drug delivery and laid a good foundation for the study of COFs as drug carriers.