Cyclodextrin Metal-Organic Framework As Carriers For Active Small Molecules

Metal-organic frameworks(MOFs)are organic-inorganic hybrid crystallines that possess many favorable merits,including high specific surface area,abundant nanopores,unsaturated metal sites,and structural and functional diversity.MOFs have been widely applied in gas adsorption and separation,catalysis,drug delivery,and bioimaging.Cyclodextrin-based metal-organic frameworks(CD-MOFs),discovered in 2010 by Stoddart et al.,are highly biocompatible,degradable,and renewable porous materials.Nowadays,the applications of CD-MOFs remain to be explored and are limited by their inherent crystal structure-induced fragility that results in difficulties in material processing.In this dissertation,we first prepared the flexible CDMOFs/cellulose composites(CelluMOFs)through an in-situ growth process.We also explored the applications of CD-MOFs and CelluMOFs in fragrance encapsulation,VOCs adsorption,CO2 capture,drug delivery,and contrast-enhanced biomedical imaging.The main findings and contributions of this dissertation include:1.Fabrications and applications of γ-CD-MOF nanocrystals for the encapsulation and controlled release of fragrant molecules.Low toxic and highly efficient nanocarriers are highly demanded in the fragrance and perfume industry.In the first part,we first explored the use of green and nontoxic γ-CD-MOF as fragrance carriers.Cytotoxicity assay showed that γ-CD-MOF was biocompatible materials similar to γCD that are classified as prebiotics in the food industry.Compared with γ-CD,the γCD-MOF nanocrystals showed three times higher encapsulation capability for the two ester-type fragrances and superior sustained release for all of the tested fragrances.The host-guest hydrophobic and hydrogen-bonding interactions between the fragrant molecules and the γ-CD units/γ-CD-MOF were studied by Fourier-transform infrared spectroscopy and molecular docking.We found that hydrogen bonds played an important role in the binding of polar ester fragrances and γ-CD-MOF.The release profiles of the two ester-type fragrances were linear and can be fitted well by the zeroorder model,whereas those for terpene-type fragrances showed an initial burst release fitting the Weibull model.2.Design of multifunctional nanoprobes based on the host-guest interactions between β-CD-MOF and small molecular probes.Low toxic and highly sensitive contrast agents are highly required in clinical diagnosis of disease.In the third part,we observed the morphology of β-CD-MOF gradually turned from lamellar to oblate in aqueous solution.By controlling the degradation time,we obtained β-CD-MOF nanoparticles with optimal morphology and size for in vivo applications.The circulation time in vivo can be modulated by the self-assembly of β-CD-MOF and the hydrophilic Ad-PEG5K chains.Through host-guest interaction,we produced β-CDMOF-based fluorescent nanprobe(β-CD-MOF/Ad-Cy5),MRI contrast agent(β-CDMOF/Ad-(Gd-DOTA))and CT contrast agent(β-CD-MOF/Ad-ATIPA).The relaxivities of β-CD-MOF/Ad-(Gd-DOTA)was 3.8 times than that of the gadoteridol used in clinic.Both the β-CD-MOF-based MRI contrast agent and CT contrast agent provided better imaging of blood pools and organs in vivo compared to their corresponding small molecular contrast agents.Compared with the gadoteridol used in clinic,the β-CD-MOF-based MRI contrast agent showed similar or lower levels of Gd(Ⅲ)in main organs and tissues one week after the injection.Therefore,the β-CD-MOFbased MRI contrast agent was an ideal blood pool contrast agent.3.In-situ growth of γ-CD-MOF on various natural cellulose fiber-based materials(CelluMOFs).The application of CD-MOFs was constrained by the crystal brittleness.Cellulose fiber-based materials have been widely used in daily life for a broad application owing to their intrinsic merits such as availability,eco-friendly,good processability,and outstanding physical-mechanical properties.In the second part,we firstly introduced a green,facile and universal method for the in-situ growth of γ-CDMOF in cellulose fiber-based materials(CelluMOFs).The resulting CelluMOFs had high porosity,up to 50 times larger specific surface area,and enhanced loading capacities to functional molecules(essential oils,antibacterial agents,and active drugs),23-36 times higher loading contents of those of pristine fibers.The CelluMOFs also exhibited high adsorption capabilities to volatile organic compounds and carbon dioxide.Moreover,the CelluMOFs textiles loaded with a model drug(doxorubicin)showed a steady release profile and deep skin permeation capability.These CelluMOFs combined the advantages of both cellulose fibers and γ-CD-MOF,which greatly extend their applications in the fragrance industry,antimicrobial,pollutant removal,and biomedical textiles.