Top-down Fabrication Of Monodisperse Gold Nanoparticles And Their Biomedical Applications

Recently,gold nanoparticles have intrigued considerable attention owing to their tunable localized surface plasmon resonance（LSPR）properties and excellent biocompatibility.They have been developed for many different applications such as cancer therapy,medical imaging and drug delivery in the field of biomedicine.Nowadays,gold nanoparticles are mostly obtained by chemical reactions in solution.These bottom-up methods have the advantages of low cost and high production efficiency,but it is difficult to accurately and independently control the shape,size,and composition of nanoparticles.To some extent,the disadvantages hinder the application of gold nanoparticles,since the physical and chemical properties of gold nanoparticles are closely related to their shape,size,and composition.In order to solve this problem,we turned our attention to the top-down methods based on micro-nanofabrication technology.Compared with the bottom-up methods,these methods have the characteristics of repeatability and controllability.The shape,size and composition of the nanoparticles can be precisely controlled by changing parameters,which means that we can fabricate nanoparticles according to our needs.Among the commonly used top-down methods,nanoimprint lithography has the advantages of high resolution,shape-controlled,low cost,and high efficiency,making it possible for being applied in mass production.This technology has an opitimistic prospect of application in the field of biomedicine.In this paper,we developed a simple and repeatable approach based on ultraviolet imprinting triple-layer resist process to prepare monodisperse gold nanoparticles.In combination with other micro-nanofabrication technologies such as dry etching and vacuum evaporation,monodisperse disk-like gold nanoparticles were successfully fabricated.The PEG-modified gold nanoparticles exhibited good dispersion and stability.The nanoparticles showed strong absorption in the wavelength region from 1000-1400 nm which belongs to the second near-infrared（NIR-II）window.The maximum absorption wavelength was around 1143 nm.The molar extinction coefficient of the nanoparticles at 1064 nm was calculated to be 4.24×10¹¹ M^-1 cm^-1,showing good light-response capability.Next,we experimented on two kinds of cells（4T1 and L02）to investigate the safety of nanoparticles.The results of MTT tests showed that the gold nanoparticles have low cytotoxicity and good compatibility.Computed tomography（CT）imaging is one of the most common clinical diagnostic imaging methods.Gold nanomaterials can be used as contrast agents for CT imaging due to their strong X-ray absorption capabilities.In this paper,CT imaging studies of the prepared gold nanoparticles were performed both in vivo and in vitro.The results showed that our gold nanoparticles have a good contrast enhancement effect.The CT imaging quality of the tumor can be effectively improved with the increase of the concentration of gold nanoparticles.In addition,in this article we investigated the application of gold nanoparticles in photothermal therapy by testing their photothermal effect in vitro and in vivo.The experimental results showed that the gold nanoparticles prepared can quickly and efficiently absorb the laser and convert it into heat energy.Under the irradiation of near-infrared light at 1064 nm,the temperature of the tumor can be increased by about 17℃in only 2 minutes.Tumor cells can be killed at this temperature.By monitoring the changes of temperature during the process of laser irradiation,real-time infrared thermal imaging of the tumor can be realized.Moreover,our nanoparticles had no obvious deformation after being irradiated by laser.It means that the gold nanoparticles can maintain stable performance during long-term use.In short,the gold nanoparticles we prepared can effectively enhance the contrast of CT images,and at the same time they have good photothermal properties.This work may provide a new idea for the integration of cancer diagnosis and treatment.