Synthesis And Properties Of Multifunctional Nanocomposites For Bioimaging

Noninvasive imaging and minimally invasive in-vivo bioimaging techniquesare valuable tools in the arsenal of clinical diagnostics. Many types of bioimaging areavailable, spanning from techniques that enable whole-organism anatomical imaging（e.g., magnetic resonance imaging, MRI） to others that provide specific molecularimaging （e.g., optical fluorescence） at subcellular resolution. Such tools are expectedto be pivotal for advancing early-stage cancer diagnosis, guided stem cell therapies,drug delivery, pathogen detection, gene therapy, image-guided surgery, and cancerstaging, in addition to many other clinically relevant procedures, diagnostics, andtherapies.No matter which bioimaging technique, its continuous development reliesgreatly on the improvement of corresponding contrast agents. On the one hand, thepractical application in clinical diagnostics requires the contrast agents to be of highsensitivity, biocompatibility, non-toxicity and can show images with high spacialresolution. On the other hand, the preparation of novel contrast agents is not onlyhelpful to the advancement of currently existed bioimaging techniques, but also theemergency and evolution of new techniques.Currently, any single imaging technique has its own advantages anddisadvantages, whereas novel multifunctional contrast agents can joint differenttechniques together to achieve much better performance. In that case, one can obtain awealth of very useful information in single-dose rather than many tediouslyprocedures, which not only saves time but also palliate the patient’s suffering. As aresult, the preparation and modification of contrast agents are of great significance.Optical fluorescence imaging is one critical component of modern bioimagingtechniques. Contrast agents used in this technique include rare earth materials, metalclusters, carbon dots and so on. But these contrast agents have the disadvantages suchas high toxicity, low biocompatibility and functional singleness.To improve the biocompatibility of contrast agent, chitosan （a kind ofbio-maromolecule） is introduced in the preparation system. The as-prepared chitosan-fluorescent hybrid contrast agents have low toxicity and much improvedbiocompatibility. On the other hand, chitosan can be used as a cost-effective moleculeprecursor to fabricate contrast agent such as carbon dots. In the end, magneticmaterials can be added to obtain multifunctional contrast agents.In chapter2, we reported a novel and mild method for one-step synthesis ofchitosan/NaGdF₄:Eu³⁺nanocomposites. The luminescent Eu³⁺ions and magneticresonance imaging （MRI） contrast agent Gd³⁺ions were incorporated to thesebiocompatible nanocomposites. The resultant nanocomposites exhibited strongfluorescence and attractive magnetic features. The nanocomposites also have purehexagonal phase with uniform size of about65nm. FT-IR spectra revealed that thesenanocomposites were successfully coated by hydrophilic chitosan, whose aminegroups conferred the nanocomposites excellent dispensability in aqueous solution.Besides, the MTT assay and laser confocal microscopy images have confirmed thegood biocompatibility of the nanocomposites. These results indicated that theas-prepared nanocomposites could be used as an excellent targeted imaging agent inbiological fields.In chapter3, a facile approach to prepare Ag cluster-encapsulated chitosanhybrid nanospheres and Eu³⁺, Gd³⁺-encapsulated chitosan hybrid nanospheres isdeveloped by utilizing ethanol-aided counterion complexation in aqueous solution.The obtained hybrid nanospheres have not only the loading space provided by thechitosan spherical matrix for loading multiply materials but also unique fluorescentproperties provided by the encapsulated Ag clusters and Eu³⁺, even more attractivemagnetic features from Gd³⁺. Besides, these hybrid nanospheres possess goodbiocompatibility and optical stability in physiological environment. It is demonstratedthat hybrid nanospheres can be internalized by MC3T3cells and Cal-27cells, andhence act as labeling agent in cell imaging by optical microscopy.In chapter4, high quality CdSe/EuxSey hybrid nanocrystals were preparedthrough two methods. The photoluminescence of hybrid nanocrystals was tunablefrom blue to deep red by varying the different amount of rare earth in quantum dots（QDs） as well as the synthesis method. The resultant hybrid nanocrystals weremonodisperse of which sizewas controllable from2.55nmto5.86nm. Furthermore, ithas been proved that the hybrid nanocrystals were of cubic crystal structure with thehost of CdSe QDs. And the lanthanide ions were incorporated into the CdSe crystallattice successfully. Finally we have developed a general and simple microwave synthesis method to produce photoluminescent carbon dots with chitosan as acost-effective molecule precursor. Through TEM, XPS, XRD and FT-IR, wecharacterized the size、crystal structure and chemical composition of as-preparedcarbon dots. The as-prepared carbon dots present very good fluorescence property. Itis found that fluorescent emission peaks of samples shifted to longer wavelengthswith increasing excitation wavelength. Besides, the photoluminescence intensity ofthe carbon dots synthesized here is pH dependent, its intensity increases as theenvironmental pH decrease in the range of4-9, and this change is reversible. Thisphenomenon indicates the as-prepared carbon dots can be used as pH sensors. In theend the MTT assay confirmed the good biocompatibility and low toxicity of theas-prepared carbon dots.