Synthesis Of Quantum Dot Nanomaterials And Their Application In The Detection And Treatment Of Influenza Viruses

Influenza viruses are serious zoonotic pathogens that continue to cause pandemics in several hosts.Influenza virus infections cause millions of deaths and huge economic losses each year posing a huge challenge not only to global public health security,but also to global economies.Although vaccination is currently the preferred method of response to an influenza pandemic,vaccines can only be used for prophylactic application.In addition,high-frequency mutations due to influenza virus antigenic drift,which limits the timeliness of the vaccine.And there are long production cycle,prone to allergic reactions and other problems.Therefore,antiviral drugs are urgently needed in the long period between the rapid evolution of the virus and the development of an effective vaccine.Current anti-influenza viral drugs can be broadly classified into three categories: M2 ion channel inhibitors,NA inhibitors and viral polymerase inhibitors.Despite the considerable antiviral ability of these clinical agents,there have been increasing reports of drug-resistant mutations of influenza viruses in recent years.In addition,long-term use of M2 ion channel inhibitors or NA inhibitors can exhibit neurological side effects.Therefore,the development of novel anti-influenza viral drugs is of great importance for the control of the epidemic.Apart from antiviral drugs,early diagnosis of the pathogen at the beginning of an outbreak play a crucial role in the control of the epidemic.Excitingly,with the rapid development of nanotechnology and nanoscience,in particular quantum dot nanomaterials and their unique physicochemical properties,they have great potential for virus detection and antiviral therapy.The development of rapid and highly sensitive biosensors and antiviral drugs using nanotechnology show great promise for future viral pandemics control.This thesis is based on the design and synthesis of quantum dot nanomaterials and the use of quantum dot nanomaterials to develop highly sensitive diagnostic methods to support the monitoring of future diseases,as well as the development of novel antiinfluenza virus nanomedicines and the study of their antiviral mechanisms,to provide new ideas and theoretical support for the development of novel antiviral nanomedicines.Details of the full research paper are summarized below:1.Synthesis of quantum dot nanospheres and their application for highly sensitive detection of influenza virusQuantum dots nanospheres were synthesized using polystyrene nanospheres as a template,QDs were absorbed on the surface of polystyrene nanospheres through a simple polyelectrolyte-mediated surface modification,and then silica was encapsulated on the surface through a layer-by-layer embedding strategy to ensure both the fluorescence stability of QDs in various buffers and the biocompatibility of the nanospheres.The synthesized fluorescence QDs nanospheres with high fluorescence quantum yield and homogeneous size can be used as novel fluorescent signal output materials.And then the magnetic beads were prepared as reaction carriers to avoid repeated centrifugation operations and to further simplify the experiment process,and then designed a fluorescent immunoassay suspension array platform with specific and sensitive detection of influenza virus.The fluorescence intensity of the newly synthesized quantum dot nanospheres is 14 times higher than that of quantum dots,and the resistance to photobleaching is higher than that of commercial time-resolved europium-doped fluorescent nanospheres.The new suspension array was constructed using the synthesized quantum dot nanospheres as the signal output molecule for the highly sensitive detection of influenza virus H5N1 with a detection limit of 25 PFU/m L.The biosensor was specific and showed no cross-reactivity with influenza viruses subtypes H1,H3 as well as NDV and IBDV.2.Antiviral effects and mechanisms of glycyrrhetinic acid-based carbon quantum dots against influenza virusesIn this study,a kind of highly dispersibility CDs were synthesized from glycyrrhizic acid(GA),a triterpenoid saponin extracted from the traditional Chinese herbal medicine glycyrrhiza glabra using simple dry heating method.The formation of GA-CDs through dehydration,polymerization,carbonization,and surface passivation.And the results showed that GA-CDs have high dispersibility,narrow size distribution and average size was 4.2 nm.Compared with glycyrrhizic acid alone,GA-CDs exhibit superior solubility and significantly improve the antiviral property against IVA.Further studies showed that the antiviral activity and water solubility were closely related to the reaction temperature,and under optimal reaction conditions,20 μg/m L of GA-CDs significantly inhibited the proliferation of influenza virus.However,the original glycyrrhizin did not show any antiviral effect even at 200 μg/m L.Investigation of the mechanism revealed that GACDs against IVA mainly through inhibiting virions internalization,replication of viral genome,neuraminidase activity and host inflammatory responses.Finally,in a mouse model,GA-CDs can significantly alleviate the clinical symptoms,decrease mortality,lung viral titers and improved survival rates.At the same concentration,the original drug had almost no antiviral effect.