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

Gold nanorods (AuNRs) are promising for remote neuronal activation via photothermal effects, but their systemic toxicity when delivered ocularly is unclear. We assessed the systemic safety of intravitreally injected AuNRs in mice over 32 days, testing three formulations: 25-nm diameter Thy-1 conjugated AuNRs (default), 10-nm diameter Thy-1 conjugated AuNRs (effect of size), and 25-nm diameter bare AuNRs (effect of surface chemistry). Thy-1 conjugation aimed to target retinal neurons specifically. Mice received AuNR injections or phosphate-buffered saline as a control. Hematological parameters, serum biochemistry, and body weight were evaluated at 2-, 8-, and 32-days post-injection. Thy-1 conjugated AuNRs did not significantly alter serum biochemical indices or blood counts compared to controls, indicating no systemic toxicity. In contrast, mice injected with bare AuNRs showed a 23% increase in uric acid levels ( = 0.0018), suggesting potential systemic effects due to lack of targeted delivery. Age influenced monocyte concentration, and cholesterol level, while sex differences were noted in body weight and several hematological and biochemical parameters. Our findings suggest that intravitreally injected Thy-1 conjugated AuNRs are systemically safe up to 32 days post-injection, emphasizing the importance of targeted nanoparticle design to mitigate potential toxicity.