Study On The Preparation And Application Of Amphiphilc Cellulose Copolymers And Their Self-Assembled Nanomicelles

The polymeric micelles, which are commonly composed by synthetic block amphiphliccopolymers, have been established great potential application in the field of drug or genedelivery. However, the large-scale application of many synthetic block copolymers is limitedby their high prices and potential biotoxicity. Therefore, there has been a growing interest indeveloping amphihilic copolymers from natural polysaccharies. It’s well known that celluloseis one of the most abundant natural polysaccharides in the world. However, thecellulose-based amphiphilic derivatives have not been efficiently exploited due to itsinsolubility in water and common organic solvents. In respond to the need of efficientlyconversing cellulose to value-added products, this thesis is mainly focused on the design andpreparation of amphiphilic cellulose polymers and their self-assembled nanomicelles.Additionally, the potential application of cellulose-based nanomicelles in the fields of drugdelivery, bioimaging and sensing was also investigated. This work would not only develop thegreen and cheap micelle-forming materials from natural resources, but also offer analternative way for the value-added conversion of agricultural and forest waste biomass. Aseries of innovative researches were carried out as follows:1. The amphiphilic cellulose copolymers with excellent biodegradable and biocompatibleproperties were homogeneously prepared in the green solvent of ionic liquids. Three kinds ofhydrophobic aliphatic polyesters, polylactide (PLA), polycaprolactone (PCL) andpolydioxanone (PPDO) were grafted onto the backbone of cellulose and cellulose’swater-soluble derivatives through the ring opening polymerization, respectively. It was foundthat the cellulose-based amphiphilic copolymers could self-assemble into core-shell structuredmicelles in aqueous water. The hydrophobic core was formed by the biodegradable sidechains such as PLA, PCL and PPDO, while the outer shells were formed by the main-chain ofcellulose. The self-assembly behavior of these amphiphilic cellulose derivatives in aqueouswater was found to be affected by their molecular structure, especailly the degree ofsubstitution of hydrophobic groups. The MTT assay showed that these amphphilic cellulosemicelles were safe to be applied in biological system.2. Through activation of carbonyldiimidazole, the acylation between hydroxyethylcellulose and long-chain fatty acid were successfully carried out in the solvent of DMSO atroom temperature. The obtained derivatives have excellent self-assembly behavior and theircritical micelle concentrations were as low as0.0019mg/mL and0.0016mg/mL, respectively, indicating that these kinds of micelles have good anti-dilution stability. It was also found thatthe cellulose-based micelles could efficiently encapsulate the hydrophobic functional moietiesof β-carotene and make them slowly released in the aqueous medium, which means thenanocarriers may be used as cosmetics or food additives.3. A series of cellulose-based hydrophobic associating polymers with different DS valuesand chain lengths were successfully prepared by homogeneous acylation of microcrystallinecellulose with long-chain acyl chloride. It was found that these cellulose derivatives couldself-assemble into monodispersed nanoparticles with spherical shapes in aqueous solution andtheir diameters can be controlled by adjusting the chain length of hydrophobic groups.Additionally, the hydrophobic modified hydroxyethyl cellulose derivatives (HMHEC) wereeasily synthesized by introducing hydrophobic moieties (long-chain alkyl groups) into thebackbone of HEC. The HMHEC could form near spherical particles with diameters in therange of20-30nm.4. The novel and biodegradable cellulose-based nanomicelles were used to encapsulatethe hydrophobic anticancer drug of paclitaxel (PTX) to overcome its drawbacks such astoxicity, insolubility in aqueous water, and low biological availability. It was found that thecellulose-based nanomicelles can uptake PTX with high encapsulation efficiency up to90%,and the release behavior of PTX was in a steady and slowly pattern. The in vitro anti-tumoractivity was assessed using the Human Cervix Carcinoma cells (Hela) and hepatoma cell(Hepg2) by MTT test and was compared to the commercial formulation Taxol. ThePTX-loaded nanomicelles have a similar cell inhibition rate to that of Taxol. Furthermore, cellinhibition of PTX-loaded nanomicelles was dependent on the treated time, increasing withprolonging of the treated time. The results from flow cytometry and DAPI staining indicatedthat PTX from nanomicelles could induce cell apoptosis to achieve tumor inhibition.5. The novel fluorescent amphiphilic cellulose nanoaggregates were successfullyprepared by encapsulation of hydrophobic fluorescent conjugated polymers (CPs) or quantumdots (QD) in the amphiphilic cellulose nanomicelles and their application in the field ofbioimaging was also evaluated. It was found that CPs or QD can be encapsulated into thecores of micelles with high efficiency and no obvious fluorescence quenching was observed.This fluorescent cellulose-based nanomicelles were kept stable after stored for7days at roomtemperature. The fluorescent nanomicelles were observed to be non-toxicity, and can beinternalized and imaging in live cells via cell endocytosis. Potentially, this method proposedin this part may be applied in biological cells imaging in aqueous solution.6. The common commercially available light-emitting conjugated polymers of poly(9,9-dioctylfluorene (PFO) were easily dispersed into water by efficiently encapsulatedthem in the amphiphilic cellulose nanomicelles, which could offer an alternative way to usethose common hydrophobic CPs in aqueous solution. The PFO-containing cellulose-basedmicelles were successfully used to detect trace amounts of nitroaromatics (2,4-dinitrotoluene,picric acid) in aqueous solution and the sensitivity of PFO in nanomielles was50～200higherthan that of the chromophores in organic solvent, which means the cellulose nanomicelles canbe used to develop the novel nanocarriers for sensoring and extending the application regionof CPs.