Development of composite nanoparticles composed of silica-coated nanorods and single nanometer-sized gold particles toward a novel X-ray contrast agent

Abstract

Gold (Au) is expected to function as a high contrast agent for X-ray computed tomography imaging as it has high X-ray absorptivity owing to a large atomic number compared to commercial materials such as barium and iodine. In addition, Au formation with a nanorod structure (AuNR) can be used for hyperthermia because of the enhancement of the photothermal reaction effect. The present work proposes a preparation method for core–shell nanoparticles composed of AuNR, SiO2, and a single nanometer-sized Au (sAu), toward imaging and photothermal therapy. The AuNRs (lateral size: 12.6 nm; longitudinal size: 44.9 nm) were silica-coated using a sol–gel method with tetraethyl orthosilicate, which produced AuNR/SiO2 nanoparticles with an average size of 86.9 nm. Thiol groups were introduced onto the AuNR/SiO2 nanoparticle surface by using (3-mercaptopropyl) trimethoxysilane (AuNR/SiO2-SH). The sAu nanoparticles (particle size: 2.6 nm) were produced by adding tetrakis (hydroxymethyl) phosphonium chloride as a reductant and HAuCl4 (aq) to NaOH solution. A thiol-terminated PEG (PEG-SH) aqueous solution and sAu nanoparticle colloidal solution were added in turn to the AuNR/SiO2-SH dispersed in EtOH (AuNR/SiO2/sAu-PEG). The CT value of the AuNR/SiO2/sAu-PEG particle solution was 702 HU. The CT values in tissues immediately increased after injection into mouse. Their blood retention times were 3–6 h, much longer than the few minutes of a commercial X-ray contrast agent (Iopamiron).