Construction of New Hybrid Bio-Nanomaterials and Their Applications in Disease Diagnosis and Treatment

Author:Sun Yu Huan

Supervisor:qu xiao gang


Degree Year:2019





The integration of biotechnology and nanotechnology has promoted the development of hybrid biomaterials.This combines not only the biocompatibility,specific recognition and high-efficiency catalytic properties,but also the unique electronic,optical,and magnetic properties of these hybrid materials.Based on these excellent properties,hybrid biomaterials have been widely studied and used in biological fields,including biosensor,detection and treatment of pathogenic bacteria,diagnosis and treatment of cancer,and biocatalytic reaction.The thesis focused on construction of a series of disease diagnosis and treatment systems by combination of specific properties of biomolecules with multifunctional nanomaterials.The main results are summarized as following:1.Through positive quaternized magnetic nanoparticles with single stranded DNA non-covalent electrostatic attraction,a simple and sensitive detection system has been constructed for pathogenic bacteria based on DNA amplification test.In the presence of pathogenic bacteria with a large number of negative charges,DNA can be competitively displaced from the surface of nanoparticles to the solution.After simple magnetic separation,the released DNA is transferred to the test tube for the next step of DNA amplification analysis assisted by exonuclease Ⅲ.2.Through covalent modification,chitosan can be modified on the surface of metal-organic framework nanoparticles(PCN-224).Based on this and cellulose paper,a resistant-visible band-aid for detection and selective treatment of bacterial infections has been constructed.The porous structure of PCN-224 is conducive to drug loading and delivery,and PCN-224 has better photodynamic properties than porphyrin molecules.Chitosan is used to attract negatively charged bacteria and achieve acid-responsive drug release.The colour of the bandage indicates bacterial infection(yellow)and drug resistance(red).Based on color,antibiotic-based chemotherapy and PCN-224-based photodynamic therapy are performed on treating sensitive and resistant strains respectively.3.Through hydrophobic interaction,hyaluronic acid can wrap onto hollow carbon nitride spheres.An anti-biofilm strategy in vivo combining quorum sensing inhibition and photodynamic therapy has been constructed.Hollow spheres provide multi-drug delivery capabilities to ensure that quorum sensing inhibitors and antibiotics can be released in sequence;carbon nitride spheres have the ability of photodynamic therapy,which can destroy biofilm components,kill bacteria,and synergistic antimicrobial with chemotherapy;hyaluronic acid endow such hybrid material with bacterial responsiveness,which ensure the bio-safety and targeted treatment,and conduce to the application of hybrid bio-nanomaterials into the anti-biofilm therapy in vivo.4.Through covalent modification,a telomeric G-overhang-specific DNA nano-hydrolase has been constructed,which is composed of four parts:(1)dexamethasone for targeting tumor cell nuclei;(2)complementary DNA for hybridizing with G-overhang;(3)multinuclear CeⅣ complexes for hydrolyzing G-overhang;(4)near-infrared upconversion nanoparticles for real-time tracking.The multivalent targeted NIR DNA nano-hydrolase can be traced to locate at tumor telomere and precisely digest telomeric G-overhang,resulting in telomeric DNA shortening and damage,and causing cell aging and apoptosis.5.Through covalent modification,a series of chiral amino acids with different properties can be modified on the surface of CeNPs to construct chiral nanoenzymes.A commonly used drug for Parkinson’s disease,namely 3,4-dihydroxyphenylalanine(DOPA)enantiomers are used as chiral catalytic substrates.The kinetics of eight different amino acid modified CeNPs was studied in detail.It was found that the phenylalanine modified CeNPs was optimal for the DOPA oxidation reaction and showed excellent stereoselectivity towards its enantiomers.