Applications Of Functionalized Gold Nanoparticles In Biomedical

Gold nanoparticles,with unique redox properties,surface plasmon properties and surface Raman enhancement properties,are widely applied in disease surveillance,disease treatment,bioimaging,and biosensing where the combination of gold nanoparticles with other various biomolecules are usually required in order to achieve different biological functions.The main work of this paper is to fabricate functional gold nanoparticle complexes to achieve different functions in the biomedical field,including regulating protein activities,early detection of diseases in surface Raman enhanced scattering and targeted gene transfection to achieve disease treatment.The detailed works are introduced as follows.Firstly,reversible addition-fragmentation chain transfer(RAFT)polymerization was used to synthesize pH -responsive polymers poly(2-(dimethylamino)ethyl methacrylate)(PDMAEMA)and poly(methacrylic acid)(PMAA).The polymer with a thiol group was formed from the dithioester group reduced by Ethanolamine.Then,the gold nanoparticle layers(GNPL)were modified with PDMAEMA by Au-S bond self-assembly.Finally,the cysteine-mutated Escherichia coli inorganic pyrophosphatase(PPase)and PMAA were grafted onto the surface of AuNP in a certain ratio to fabricate a ternary complex.By characterization of the amount of adsorption under different pH conditions,the optimal pH for the control of adsorption was found to be 7.0 and the optimal pH for release was 10.0.At the same time,the influence of the roughness of GNPL on the adsorption activity was explored.Exploiting the reversible changes of the characteristics of pH -responsive polymers with the pH of the surroundings,the adsorption and release of nanoparticle complexes can be controlled and repeated in three cycles,which enabled the GNPL to be recyclable.Finally,horseradish peroxidase(HRP)and PMAA were cografted on the surface of gold nanoparticles by physical adsorption.The results of adsorption and co-adsorption of the two particles in turn indicated that the two nanoparticle complexes not only could function separately,but also could work together in the process of absorb and release.This kind of functional surface utilizing the electrostatic interaction between polymers to achieve the adsorption and release of surface proteins breaks the restriction on the isoelectric point of the dependent protein when employing the interaction between protein and polymer,which largely broadened the range of applications.The reusable multifunctional bioactive surface is expected to have many potential applications in the field of biological drug loading,biological detection,molecular immobilization,and so on.Secondly,functionalized gold nanoparticles have many applications in disease detection.Among them,surface Raman enhanced scattering,based on a narrow band width,is not affected by water,and does not easily undergo photobleaching.At present,research focuses on the preparation of solid substrates and the prevention of its nonspecific adsorption.In our work,antibodies modified on gold nanoparticle layers(GNPL)and second antibodies modified on AuNP are bound by antigen to form a “solid-phase based antibody-antigen-labeled antibody” sandwich complex.This "sandwich" model is used for the detection of the early stage of prostate cancer by monitioring the amount of antigens.The results showed that GNPL is superhydrophilic and can effectively prevent non-specific adsorption.Moreover,the influence of GNPL roughness on the enhancement of SERS signal was systematically studied.At the same time,the signal intensity was detected at different antigen concentrations to find the correspondence between antigen and signal intensity.The results showed that this SERS-labeled immunodetection method using GNPL as a solid substrate can realize the detection of prostait specific antigen(PSA).Due to its advantages of easy preparation and resistance to non-specific adsorption,it is potential for the applications in SERS immunodetection.Finally,two polymer-encapsulated gold nanoparticles were synthesized by modifying the polyethyleneimine(PEI)with the cancer cells targeting molecule folic acid(FA).PEI and PEI-FA were used as reducing agents and stabilizers to synthesize PEIAuNP and PEI-FA-AuNP,respectively.The ability of DNA encapsulation of two gold nanoparticles,the transfection efficiency and transfection cytotoxicity under different N/P were studied in detail.The results showed that the transfection ability of PEI-FA-AuNP was decreased due to free carboxyl groups in folic acid.Therefore,by mixing two kinds of nanoparticles,PEI-AuNP was used to encapsulate DNA,and PEI-FA-AuNP was displayed the targeted transfection ability.Experiments showed that this two kinds of nanoparticles have the highest transfection efficiency when the ratio is 5/5,and at the same time,they showed good target transfection ability.Finally,it was proved that this transfection system can perform nuclear transfection by DNA staining techniques.This highly efficient transfection system with low toxicity is expected to have significant applications in cancer treatment.In summary,by preparing different biomolecules functionalized gold nanoparticles,various biological functions can be achieved.Gold nanoparticles can be served as a good biomolecular carrier capable of supporting proteins and regulating its activities,a SERSlabeled immunodetection substrate capable of effectively binding with labeled molecules and a gene carrier capable of complexing with DNA and realizing targeted gene transfection as well as cancer treatment.With the development of nanotechnology,the interest in the research of gold nanoparticles continues to increasing,and it is reasonable to believe that it will play an increasingly important role in the field of biomedicine including but not limited to disease diagnosis,disease treatment and biological sensing.