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Study On Polymer Modified DNA Nanostructure

Posted on:2020-09-29Degree:DoctorType:Dissertation
Country:ChinaCandidate:X M XuFull Text:PDF
GTID:1361330599461869Subject:Biomedical engineering
Abstract/Summary:PDF Full Text Request
DNA nanotechnology,as a new nanomaterials fabrication technique,has greatly promoted the integration of nanoscience and biological materials.With the advent and development of DNA origami,a variety of complex two-dimensional and threedimensional DNA nanostructures have been prepared.DNA nanotechnology allows people to precisely control the shape and size of nanomaterials at nanometer-scale invisible to the naked eye.At present,DNA nanostructures have been widely used in material and biological fields due to their easy modification,addressability and excellent biocompatibility.For example,various hydrophobic molecules can be covalently modified on DNA molecules to induce the assembly of DNA nanostructures;DNA nanostructures can be used as carriers of gold nanoparticles and anticancer drugs to achieve synergistic effects of photothermal and chemotherapy.Therefore,DNA nanostructures have tremendous advantages and potential for clinical application.However,DNA molecules are also relatively unstable,for instance,DNA nanostructures can be rapidly degraded by DNAenzymes in living systems.Based on this,we consider combining cationic polymer materials with DNA nanomaterials to modify DNA nanomaterials with polymer.In order to solve the problem of low stability in physiological solution and low cell uptake rate of DNA nanostructures,we will study the stability and cell uptake rate of DNA nanomaterials modified by polymers,so as to further promote the development of biomedical DNA nanomaterials.Specifically speaking,in this paper,we will study the interaction between DNA origami structures and protein and other synthetic polymers,as well as the stability and cell uptake of DNA nanostructures modified by polymers.It mainly includes the following contents:(1)Firstly,we constructed positively-charged protein-protected DNA nanostructures.Due to electrostatic adsorption,when DNA nanostructures were mixed with positive proteins,the positive proteins will be adsorbed on DNA origami structure to form a protein-coated shell.Protein coating can protect DNA nanostructure from DNAzyme digestion and make it more stable under low salt concentration and acid conditions.Moreover,positive charge-encapsulated DNA origami has higher cell uptake efficiency than DNA origami.(2)Secondly,polymers were modified on the DNA nanostructures by in-situ atom transfer radical polymerization(ATRP).In-situ ATRP was initiated from the initiator molecules positioned at specific sites on DNA origami,then specific shapes of polymer modified DNA nanostructures were obtained.High-density polymer layer modified on the surface of DNA nanostructures can protect DNA structures from degradation by DNA enzymes.At the same time,the G-quadruplex catalytic center was modified in the polymer-protected nano-cavity to catalyze in-situ polymerization of dopamine,realizing the construction of polymer-protected DNA nanoreactor.(3)Finally,in order to controllably construct positively-charged polymer modified DNA nanostructure,improve its cell uptake efficiency while retaining its modifiable and addressable functions,the controllable modification of cationic polymer on DNA nanostructure was realized by photo-response conversion strategy.Photo-responsive polymer were grown on specific regions on DNA origami by in-situ ATRP reaction,which were initiated at pre-designed positions on the surface of DNA origami.Under ultraviolet irradiation,protective groups were released from polymer and the positivelycharged amino groups were exposed out to form regionally cationic polymer.Highly dense amino groups will change the electrical properties of DNA origami and effectively improve its cell uptake efficiency.
Keywords/Search Tags:Bionanomaterials, DNA origami, Cell uptake, Polymer nanomaterials, Protein encapsulation, Nanoreactor
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