Bubble template synthesis of hollow gold nanoparticles and their applications as theranostic agents.

摘要

Hollow gold nanoparticle with a sub-30nm polycrystalline shell and a 50 nm hollow core has been successfully synthesized through the reduction of sodium gold sulfite by electrochemically evolved hydrogen. Such hollow gold nanoparticles exhibit unique plasmonic properties. They strongly scatter and absorb near infrared light. In this thesis we seek to understand the formation mechanism of hollow gold nanoparticles in this new synthesis process and their plasmonic properties. Also, we explore their biomedical applications as theranostic agents (therapeutic and diagnostic imaging).;A lithographically patterned electrode consisting of Ag stripes on a glass substrate was used to investigate the formation process of hollow gold nanoparticles. Ag stripes served as working electrode for electrochemically evolution of hydrogen, and adjacent glass areas provided supporting surface for hydrogen nanobubbles nucleation and growth. Hydrogen nanobubbles served as both templates and reducing agents to trigger the autocatalytic disproportionation reaction of sodium gold sulfite. The effects of applied potential and the additives in the electrolyte have been studied. It has been found that the size and size distribution of hollow gold nanoparticle are directly relative to the applied potential, i.e. the hydrogen evolution rate. It has also been found the addition of Ni2+ ions can greatly improve the size distribution of hollow gold nanoparticles that can be contributed to that the newly electrodeposited nickel metal can enhance the hydrogen evolution efficiency. Another additive, ethylenediamine (EDA) can suppress the autocatalytic reaction of gold sulfite to increase the stability of sodium gold sulfite electrolyte.;To capture such electrochemically evolved hydrogen nanobubbles, and subsequently to generate hollow gold nanoparticles in large numbers, alumina membranes were placed on the top of the working electrode. Anodic alumina membrane consists of ~200 nm pores, which provides a large surface area for the formation of hydrogen nanobubbles. By this approach, the electroless reaction can be easily separated from the electrodeposition process, and hollow gold nanoparticles can be easily collected.;Synthesized hollow gold nanoparticles exhibit unique plasmonic properties; the surface plasmon resonance (SPR) lies in the near infrared region (NIR). This is very different from the solid spherical gold nanoparticles. Three-dimensional finite difference time domain (FDTD) simulation was employed to study the plasmonic properties of hollow gold nanoparticles. It has been found that the red-shifts of SPR peaks are mainly caused by their surface roughness, and the hollow nature of these particles only plays a minor role. The surface roughness of hollow gold nanoparticles can be tuned by adjusting the pH of the electrolyte (from 6.0 to 7.0) by adding sodium sulfite. Different surface roughness (from smooth to very rough) can be readily obtained, and correspondingly, surface plasmon resonance (SPR) peaks red-shift from ~600 nm to ~750 nm.;Using hollow gold nanoparticles as multifunctional agents for biomedical applications have been explored. Two kinds of agents have been constructed. It has been demonstrated that pegylated Raman dye encoded hollow gold nanoparticles, terms as Raman nanotags, can serve as both diagnostic imaging agents and photothermal therapy agents. When illuminated by near infrared light, the enhanced Raman signal makes the hollow gold nanoparticles to become optically detectable for biomedical imaging, and absorbed light rapidly heat up the hollow gold nanoparticles which can be used to photothermal ablation therapy. The cytotoxicity evaluation using [3H] thymidine incorporation method has shown non-toxicity of the Raman nanotags. The photothermal effects of hollow gold nanoparticles have been examined by two methods: (1) by embedding hollow gold nanoparticles in tissue-like phantom environment; (2) by recording infrared images as temperature increase. The results show that hollow gold nanoparticles are capable to generate sufficiency heat for photothermal therapy. To fully take advantage of the unique hollow core space of hollow gold nanoparticles, a facile route has been develop to trap Fe3O4 nanoparticles into the hollow gold nanoparticles to form Fe3O4/Au core/shell nanoparticles. Fe3O4/Au core/shell nanoparticles possess the desirable magnetic and plasmonic properties that can be used as magnetic resonance contrast (MRI) agents and photothermal therapy agents.