Design Of DNA Self-Assembled Nanomaterials And Its Antibacte-Rial And Anti-tumor Application

In recent years,the incidence of tumors has increased,seriously threatening human life and health,and has become one of the main lethal diseases in our country.At present,the incidence and mortality of tumors are still increasing,and many researchers around the world are committed to developing accurate,rapid and effective diagnostic and therapeutic methods to treat cancer.The emergence of nanotechnology has brought new hope for the solution of these problems.In the field of biomedicine,the nanometerization of diagnostic and therapeutic reagents can not only improve their water solubility,stability and targeting,but also can use diagnostic methods such as nanoparticle imaging to monitor the therapeutic process of nanomedicine in real time,and feedback the therapeutic effect.The therapeutic effect on the disease is of great significance for enhancing the clinical treatment effect and reducing the toxic and side effects during the treatment process.At present,nano-diagnostic and therapeutic reagents for cancer mainly include inorganic materials（porous silicon,graphene,etc.）,organic small molecules（indocyanine green,Prussian blue,etc.）,the above-mentioned materials have potential cytotoxicity/low biocompatibility and organic the side effects of small molecules limit its further application.DNA nanotechnology has the advantages of strong design,simple synthesis,and functional diversity,so it is widely used to construct tumor-targeted imaging,drug delivery,and tumor treatment.In this thesis,a series of functional DNA nanoparticles were prepared using different design strategies and applied to antibacterial and anti-tumor applications,achieving remarkable results.The main research contents are as follows:（1）Highly universal metal DNA nanoparticles.The preparation method of the assembly system.In this chapter,DNA molecules and metal ions are used as templates,and the strong coordination between metal ions and single-stranded DNA is used to introduce hydrophilic drugs,hydrophobic drugs,peptides and other substances into the nanosystem.By adjusting the concentration ratio of reactants and under the reaction conditions,a series of DNA nanoparticles with stable morphology and uniform size were obtained.Hydrophilic guests can be loaded into DNA nanoparticles during the assembly process through extremely simple coordination;for hydrophobic guests,the host-guest inclusion interaction of cyclodextrin supramolecules is used to form water-soluble drugs and cyclodextrin inclusion complexes.In the same way,the corresponding DNA nano-drug particles are formed.Through the above method,vancomycin,curcumin,resveratrol,antibacterial drug PBP1 and peptides were successfully loaded,and the co-assembly of DNAzyme and metal ions was successfully realized,which confirmed the universality of the above method and is a follow-up work.Provide material support.（2）DNA self-assembly dual-function nano antibacterial material construction and its antibacterial application.In this chapter,we successfully encapsulated the well-water-soluble antibacterial drug vancomycin（VAN）in Fe²⁺and DNA co-assembled nanoparticles through the assembly method developed above,and constructed a DNA nano-drug with good antibacterial effect.Furthermore,the controllable introduction of silver ions（Ag⁺）with better antibacterial effect into the system realizes DNA self-assembled nanospheres with dual-function antibacterial properties,and further enhances the antibacterial ability of the material.The research results show that the antibacterial nanomaterial has a good inhibitory effect on Staphylococcus aureus in vitro,and the antibacterial rate can reach95%.（3）The construction of bifunctional DNA nanomaterials mediated by supramolecules and the programmed treatment of tumors.In the work of this chapter,we first coat the star drug resveratrol with good anti-tumor effect into the hydroxypropyl cyclodextrin cavity to obtain its supramolecular inclusion compound,and then use the same assembly method in（1）to construct.A dual-functional DNA nano anti-tumor material.The introduction of cyclodextrin supramolecules not only significantly enhances the water solubility of resveratrol,thereby improving its coating and delivery efficiency,but also forms a natural protective barrier to avoid the decomposition of active oxygen oxidized drugs in the process of its delivery and cell entry.After the nanoparticles enter the cell,firstly,Fe²⁺reacts with H₂O₂ in the tumor cells,triggers the intracellular Fenton reaction,rapidly produces highly toxic hydroxyl radicals（ROS）,causes tumor cells to undergo apoptosis,and then protects them from the hydroxypropyl group.The resveratrol in cyclodextrin is gradually released slowly,giving full play to its anti-tumor efficacy and aggravating tumor cell apoptosis.The above-mentioned cyclodextrin supramolecular-mediated bifunctional procedural therapy provides a new idea for the design of nano-antitumor drugs.（4）Cu-DNAzyme self-assembled nanoparticles for dual-catalytic treatment of tumors In this chapter,in order to increase the diversity of the nanosystem,we introduce functional DNA（DNAzyme）into the nanosystem.Using Cu²⁺and DNAzyme as structural units,hybrid nanoparticles with ultra-high loading capacity were prepared Cu-DNAzyme nanocomposite can effectively transport DNAzyme and Cu²⁺to cancer cells for combined catalytic therapy.The released Cu²⁺can be reduced by glutathione to Cu^+,which can then catalyze endogenous H₂O₂ to form cytotoxic hydroxyl radicals for chemodynamic therapy,while 10-23 DNAzyme can catalyze the cleavage of VEGFR2 mRNA and activate gene silencing for gene therapy.The system can effectively accumulate in tumors and exhibits an amplified cascade anti-tumor effect,providing an effective new method for the dual-catalytic tumor therapy of DNAzyme and CDT.