Construction Of DNA-Based Inorganic Nanomaterials And Investigation Of Their Applications In Biochemical Analysis And Disease Treatment

With the development of nanomedicine,inorganic nanomaterials have facilitated the intersection between different disciplines such as materials,chemistry and medicine,thus providing new ideas and research methods for the solution of problems in medical diagnostics and disease treatment.The unique optical properties of inorganic nanomaterials make them potential in imaging detection and biochemical analysis.Also,their unique structural and surface properties,such as porosity and modifiability,allow them be broadly applied in drug delivery and disease treatment.Therefore,biochemical analysis and disease treatment based on inorganic nanomaterials have opened up a new research path for disease diagnosis and treatment.However,inorganic nanomaterial is just a unit for outputting signal or producing curative effect,and they cannot specifically recognize the target molecules or disease locations.In order to improve the specificity of the detection and the effectiveness of the treatment,endowing inorganic nanomaterials with the capacity of targeted recognition is an optimistic alternative.So the design of recognition molecules is highly important in construction of functional inorganic nanomaterials.The usually happened molecular recognition pairs in biological systems are antibody/antigen,enzyme/substrate and so on.Researchers have also developed diverse organic molecules and polypeptides with recognition capability.However,these recognition molecules face multiple challenges,such as limited kinds of targets,poor solubility and poor manufacturability.Functional DNA is class of nucleic acid molecules that can bind to their targets with high specificity,which provides a promising platform for the design of nano-platform with targeting ability.Particularly,aptamer is an important kind of functional nucleic acid,which can specifically bind to their targets by folding into unique secondary or tertiary structures that accommodate the molecular structure of the target,thus leading to selective recognition of targets.Furthermore,aptamers are usually small and offer a great advantage in design,selection,chemical synthesis/modification and transportation over traditional antibodies.In recent years,aptamers have gained widespread interests in construction of nanoprobes and therapeutic systems for the application in biosensing,bioimaging,biomedical diagnosis and disease therapy.With the rapid development of nucleic acid research and nanotechnology,functional DNA,especially aptamer,is being largely employed to design functionalized nano-systems.These DNA-based nano-systems hold good potential in biochemical analysis and disease treatment.In this work,we designed several DNA-based inorganic nanomaterials through combining the functional DNA molecules with the inorganic nanomaterials.We explored the application of these functional inorganic nanomaterials in biochemical analysis and disease treatment.The main contents of this dissertation are as follows:(1)We have developed a step-by-step injection method for the one-pot synthesis of core-shell upconversion nanoparticles(UCNPs).Multiple core-shell UCNPs with different excitation and different emission have been successfully prepared,and the morphology and size of these UCNPs were uniform.Importantly,the core-shell structure greatly improved the luminous efficiency of the UCNPs.(2)We have designed a UCNPs-based ratiometric luminescent probe,and further fabricated a visual miniaturized device by fixing this probe onto the portable substrate.This visual miniaturized device can show turned visible multicolor upconversion luminescence based on the analyte-modulating Forster resonance energy transfer process under near-infrared excitation,thus providing a powerful tool for visualized assays of analytes.(3)We have designed two kinds of DNA-based upconversion nanoprobes,and further constructed a biochip-based mRNA detection device by combining these two nanoprobes with a photonic crystal-based hydrophilic-hydrophobic micropattern.The high sensitivity was realized due to the target enrichment and fluorescence enhancement effect.This device achieved highly sensitive detection,using the naked eye,of multiple mRNAs among patient samples.(4)We have developed an aptamer-functionalized porous bilayer scaffold for whole knee repair.The aptamer-bilayer scaffold can enrich the mesenchymal stem cells to the defect site and then stimulate their directional differentiation in a controlled manner.Importantly,the aptamer-bilayer scaffold can simultaneously meet the requirements for cartilage and subchondral bone regeneration in a rat knee defect-repair mode.