Systemic toxicity of intravitreally injected gold nanorods in mice: Effects of size, surface conjugation, and post-injection period

Abstract Gold nanorods (AuNRs) can potentially act as photothermal stimulators when bound to neurons. An important consideration when using nanoparticles of any type is their safety in vivo. Here, we assessed the systemic safety of intravitreally (IVT) injected gold nanorods (AuNRs) in mice over 32 days, by focusing on three formulations: 25-nm Thy-1 conjugated AuNRs, 5-nm Thy-1 AuNRs, and 25-nm bare AuNRs. Thy-1 conjugation aimed to target retinal ganglion cells specifically. Our analyses included hematological data, serum biochemistry, and body weight changes. The results showed a 23% increase in uric acid concentration in the presence of bare AuNRs (p = 0.0018) and a 3% reduction in body weight in the presence of 25-nm Thy-1 AuNRs (p = 0.0230). Age influenced monocyte concentration, total bilirubin, cholesterol, and chloride levels, while sex differences were noted in body weight and several hematological and biochemical parameters. These results suggest that IVT-injected Thy-1 AuNRs may not induce systemic toxicity for up to 32 days, highlighting the importance of targeted delivery to mitigate potential toxicity.