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

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 thiolterminated 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).