Synthesis And Biomedical Application Studies Of Multifunctional Metal-Graphene Nanocapsules

Graphene nanomaterial,a kind of novel nanomaterial with superior optical,thermal,electrical and mechanical properties,has been extensively studied in various fields including electronics,energy,catalysis,sensing and biomedical fields.The graphene nanocapsule composite material is a combination of different materials(such as drugs,nanoparticles,polymers,oxides and cells)wrapped in graphene.It has more functions and better performance than individual graphene,showing great promise in micro/nano motors,biosensing platforms,bioimaging agents,drug delivery systems,potential tumor treatment alternatives,environmental remediation platforms,advanced batteries and novel supercapacitors.Up to now,preparation methods for graphene nanocapsules mainly include electrostatic self-assembly,layer-by-layer self-assembly,aerosol-phase method,hydrothermal method,emulsification method,covalent bonding and chemical vapor deposition(CVD)methods.Among them,the CVD method is one of the most promising techniques due to the following aspects:(1)It can be carried out under medium temperature or high temperature,normal pressure or vacuum conditions.(2)Plasma and laser-assisted technologies can be used to promote the reaction.(3)The chemical composition of the coating can be regulated by the gas phase composition.(4)It can effectively control the density and purity of the coating.(5)It can be deposited on complex structures(organic,inorganic,rigid,flexible,flat,three-dimensional,dense or porous).However,it is a huge challenge to prepare metal graphene nanocapsules with thin graphene layer,high material purity,controllable size and rich functions,this challenge can be solved to a certain extent by taking advantage of CVD method.In this paper,we have synthesized a series of versatile metal graphene nanocapsules by CVD method,which realizes multi-phase detection,interface catalysis,rapid Raman imaging and tumor theranostics.The specific research content is as follows:Based on the functional designability of metal graphene nanocapsules,we have prepared six kinds of metal graphene nanocapsule materials with uniform size and different functions by CVD method via adjusting the amount of precursor metal salt,reaction temperature and carbon atom deposition time,including gold graphene nanocapsules(Au@G),N-doped gold graphene nanocapsules(Au@NG)cobalt platinum graphene nanocapsules(CoPt@G),cobalt ruthenium graphene nanocapsules(Co Ru@G),cobalt rhodium graphene nanocapsules(Co Rh@G)and cobalt iridium graphene nanocapsules(Co Ir@G).Metal graphene nanocapsules with different metal core compositions have different properties,Au@G and Au@NG have good surface-enhanced Raman scattering performance and the other four metal graphene nanocapsules,different functional applications can be further realized combining the unique physical and chemical properties of the graphitic shell.Based on non-hydrophilic and non-lipophilic properties of the graphene shell,simultaneous two-phase surface enhanced Raman analysis and interfacial catalysis applications can be realized;Based on the large specific surface area and easy functionalization of the graphene shell,superior water-soluble metal graphene nanocapsules are obtained with the modification of polyoxyethylenestearyl ether,cellular and in vivo rapid Raman imaging analysis as well as tumor theranostics can be realized.Au@G had the ability to self-assemble and enrich analytes at the incompatible two-phase interface.We applied it to the simultaneous Raman detection of analytes in the two phases.Due to the non-hydrophilic and non-lipophilic nature of graphene,without the addition of surfactants.Au@G could self-assemble into a dense film at the two-phase interface,thereby generating dense plasma hot spots and increasing the Raman enhancement coefficient.At the same time,the graphene shell of Au@G could simultaneously enrich analytes from the two phases through?-?and p-p interactions.The Raman characteristic peaks of graphene in Au@G could be used as an internal standard to improve the accuracy of Raman quantitative analysis.We used Au@G to perform simultaneous detection and quantitative analysis of crystal violet and 9,10-bis(phenylethynyl)anthracene in two phases and extended it to bovine serum and mouse blood models.Both had achieved good results.The results showed that Au@G had the ability to simultaneously detect multiple analytes at the liquid-liquid interface,which was expected to be applied to more clinical tests.We further expanded the types of graphene nanocapsules,N-doped gold graphene nanocapsules(Au@NG)were obtained using amino acids to replace methane as the carbon source,and rapid Raman imaging analysis was realized.Firstly,Au@NG was obtained through the screening of nitrogen-containing carbon sources and precursor metals as well as optimization of synthesis conditions,showing very strong Raman signal in the Raman-silent region(1800 cm^-1?2800 cm^-1).The formation of C?N bond in the graphene shell of Au@NG was proved by characterization,and the formation mechanism of C?N bond was discussed preliminarily.Secondly,the quantitative analysis of crystal violet was realized based on the excellent surface-enhanced Raman analysis performance of Au@NG,and the Raman characteristic peak located in the Raman-silent region was used as a non-interference internal standard to improve the accuracy of the Raman quantitative analysis.Finally,we used Au@NG to achieve rapid Raman imaging of cells and C.elegans,which was expected to improve the limitations of Raman imaging with slow speed.Finally,we used CoPt@G to construct a nanomotor driven by a magnetic field and H₂O₂ to enhance tumor targeting and penetration.Utilizing its excellent photo-thermal performance,the efficient ablation of solid tumors was realized.The CoPt@G graphene shell could effectively protect the stability of the CoPt core and prevent it from being decomposed in the body to produce Co²⁺and Pt²⁺avoiding cytotoxicity.In addition,the graphene shell was also an excellent photothermal material and could be used as a Raman label.The core of CoPt@G had magnetic,catalytic and photothermal capabilities,and could be used for nuclear magnetic and photothermal imaging.We used magnetic field navigation to promote tumor targeting.After reaching the tumor tissue,CoPt@G catalyzes H₂O₂ to produce O₂ to obtain the driving force,thereby enhancing the spread of CoPt@G in the tumor.In the process of tumor treatment in mice,the amount of CoPt@G in the tumor is three times that of under the magnetic field and H₂O₂ than without the magnetic field and H₂O₂.In the cell experiment,the amount of CoPt@G entering the cell under the driving force is 6.9 times that without the driving force.During the treatment,the tumor growth of the mice was well inhibited under the dual-drive condition.CoPt@G provided new inspiration and opportunities for advancing cancer diagnosis and treatment.