Fabrication Of Monodisperse Metal Nanoparticles With Controllable Morphology For Biomedical Applications

Metal nanoparticles present newfangled physical and chemical properties,offering unique effects in the field of biomedicine that are different from traditional drugs and mediators.In the development of biomedical applications of metal nanoparticles,how to obtain metal nanoparticles is the primary problem.At present,metal nanoparticles are mostly formed by bottom-up methods such as precipitation method,sol-gel method,sol-thermal method.However,metal nanoparticles prepared by bottom-up methods suffer from the polydispersity in size,shape and component,and it is difficult to form complex shapes and synthesize easily reactive materials.Thus hindering the application of metal nanoparticles in biomedical field.As the fast development of nanotechnology,top-down methods represented by micro-nanofabrication technology gradually come into people's view.According to their technical characteristics,top-down methods offer high consistency and high controllability on size,shape and component of metal nanoparticles.And it is capable to fabricate metal nanoparticles with special shapes and materials that are difficult to be synthesized by traditional methods.Among all the commonly used top-down methods,nanoimprint lithography offers the potential in mass production of metal nanoparticles by the advantages of ultra-high resolution,low cost,high consistency and high through-output,making it possible for metal nanoparticles to be industrially applied in the field of biomedicine.According to the deformation modes of imprint materials,nanoimprint lithography can be divided into thermal nanoimprint lithography and ultraviolet nanoimprint lithography.For the sake of fabricating metal nanoparticles with high efficiency and high quality,we made some improvement to the existing nanoimprint processes.For thermal nanoimprint lithography,we improved the existing mold and equipment.A nickel mold with low surface energy was fabricated and a rapid thermal nanoimprint apparatus through induction heating of nickel mold was developed.Utilizing the improved mold and equipment,a fast and high quality duplication of nano-patterns from master mold was achieved.For ultraviolet nanoimprint lithography,a hybrid nanoimprint-soft lithography was developed,in which a hybrid mold composed of elastic support layer and rigid structure layer was used.The hybrid mold offered high resolution and wafer scale processing capability while maintaining good conformal contact with the substrate.In addition,we studied the impact of imprint parameters on the imprint effect and obtained a set of empirical methods to reasonably regulate the residual layer thickness according to the actual situation.Based on the improved nanoimprint process,we developed three feasible schemes to fabricate metal nanoparticles including thermal imprinting thermoplastic polymer film process,ultraviolet imprinting double-layer resist process and ultraviolet imprinting triple-layer resist process.Through the actual test comparison,ultraviolet imprinting triple-layer resist process was the best method to fabricate metal nanoparticles under our existing experimental conditions.Furthermore,we proposed a universal method for the fabrication of nanoparticles.Utilizing this method,it was capable to precisely regulate the size,shape and component of nanoparticles,making it possible to fabricate nanoparticles with shapes,sizes and components that are difficult to obtain through the traditional methods.What's more,the fabricated nanoparticles were monodispersity in size,shape and component.Based on the as-developed top-down method to fabricate metal nanoparticles,we fabricated gold nanoparticles and iron nanoparticles,which were two representative metal nanoparticles for biomedical applications.And a series of research on their properties and biomedical applications were carried out.In the case of gold nanoparticles,we successfully fabricated disc-like gold nanoparticles with regular morphology and highly consistent shape and size.After surface modification,the gold nanoparticles showed good dispersion and stability in aqueous solution.The optical properties of the as-prepared gold nanoparticles resulting from the localized surface plasmon resonance effect were also investigated.As shown in the absorption spectrum of aqueous solution of the gold nanoparticles with a diameter of 265 nm and a thickness of 30 nm,the main absorption band of the as-fabricated gold nanoparticles was in the near infrared zone ?(1000-1400 nm wavelength).And the extinction coefficient at 1064 nm wavelength was 22.9 L g-1 cm-1.The strong ability of extinction made the as-fabricated gold nanoparticles have enormous potential in bioimaging.The photothermal conversion efficiency of the prepared gold nanoparticles under the irradiation of 1064 nanometer wavelength laser was calculated to be 16.0%,showing a good photothermal conversion effect.Moreover,the gold nanodiscs showed good stability under laser irradiation.They would not deform after laser irradiation due to the self-assembly of gold under local high temperature.Therefore,the as-fabricated gold nanoparticles were capable to exert better photothermal conversion effect in long-term usage,offering great potential in photothermal therapy of cancer.In the case of iron nanoparticles,disc-shaped iron nanoparticles with regular morphology and highly consistent shape and size were successfully fabricated.Utilizing silica and gold as the protective layers covered on the surfaces of iron discs,the iron was well protected from being oxidized in practical use,improving its stability in the internal and external environment of organisms.After surface modification,the iron nanoparticles showed good dispersion and stability in aqueous solution.In terms of magnetic properties,the coercivity of the prepared iron nanoparticles was measured to be 20.1 Oe,showing no remanence.The saturation magnetization of the prepared iron nanoparticles was measured to be 197.7 emu/g,showing a strong magnetism.In addition,the as-prepared iron nanoparticles showed low cytotoxicity and good biocompatibility,which was suitable for further practical application in vivo.Based on this,we investigated the performance of the prepared iron nanoparticles in magnetic resonance imaging.The T2 relaxivity of the fabricated iron nanoparticles was calculated to be 75.998 mM-1 s-1,offering a good contrast effect in magnetic resonance imaging both in vitro and in vivo.It was indicated that the as-fabricated iron nanoparticles could be used as a good T2 contrast agent for magnetic resonance imaging.