Gold nanoparticles (Au NPs) are a potential x-ray computed tomography (CT) contrast agent. A biocompatible and bioinactive surface is necessary for application of gold nanoparticle to CT imaging. Polyethylene glycol (PEG)-attached dendrimers have been used as a drug carrier with long blood circulation. In this study, the Au NPs were grown in the PEGylated dendrimer to produce a CT contrast agent. The Au NPs were grown by adding gold ions and ascorbic acid at various equivalents to the Au NP-encapsulated dendrimer solution. Both size and surface plasmon absorption of the grown Au NPs increased with adding a large number of gold ions. The x-ray attenuation of the Au NPs also increased after the seeded growth. The Au NPs grown in the PEG-attached dendrimer at the maximum under our conditions exhibited a similar CT value to a commercial iodine agent, iopamidol, in vitro. The Au NP-loaded PEGylated dendrimer and iopamidol were injected into mice and CT images were obtained at different times. The Au NP-loaded PEGylated dendrimer achieved a blood pool imaging, which was greater than a commercial iodine agent. Even though iopamidol was excreted rapidly, the PEGylated dendrimer loading the grown Au NP was accumulated in the liver.
Recently, we demonstrated that loading of HAuCl(4) in poly(ethylene glycol) (PEG)-attached poly(amidoamine) (PAMAM) G4 dendrimers and subsequent reduction with NaBH(4) yield dendrimers encapsulating gold nanoparticles (Au NPs), which have photoinduced heat-generating properties. This study was undertaken to enhance photothermal properties of the Au NP-incorporated PEG-attached dendrimers by growing Au NPs in the dendrimers. Repeated loading of HAuCl(4) in the PEG-attached dendrimers and subsequent reduction with NaBH(4) enhanced the surface plasmon resonance, indicating that Au NPs were grown in the PEG-attached dendrimers using that procedure. Transmission electron microscopy (TEM) analysis revealed that the size of Au NPs formed in the dendrimers increased with the number of repetitions of HAuCl(4) loading and subsequent reduction in the dendrimers, although the size distribution of the Au NPs remained narrow. The photoinduced-heat generation capability of the Au NPs-encapsulating dendrimers increased as the Au NPs grew. These dendrimers with Au NPs exhibited strong cytotoxicity against HeLa cells under visible light irradiation. The result demonstrates that PEG-attached dendrimers encapsulating the grown Au NPs might be useful as devices for target-specific therapy when used with light irradiation.
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