Long-term in vivo biodistribution imaging and toxicity of polyacrylic acid-coated upconversion nanophosphors

Rare-earth upconversion nanophosphors (UCNPs) have become one of the most promising classes of luminescent materials for bioimaging. However, there remain numerous unresolved issues with respect to the understanding of how these nanophosphors interact with biological systems and the environment. Herein, we report polyacrylic acid (PAA)-coated near-infrared to near-infrared (NIR-to-NIR) upconversion nanophosphors NaYF4:Yb,Tm (PAA-UCNPs) as luminescence probes for long-term in vivo distribution and toxicity studies. Biodistribution results determined that PAA-UCNPs uptake and retention took place primarily in the liver and the spleen and that most of the PAA-UCNPs were excreted from the body of mice in a very slow manner. Body weight data of the mice indicated that mice intravenously injected with 15 mg/kg of PAA-UCNPs survived for 115 days without any apparent adverse effects to their health. In addition, histological, hematological and biochemical analysis were used to further quantify the potential toxicity of PAA-UCNPs, and results indicated that there was no overt toxicity of PAA-UCNPs in mice at long exposure times (up to 115 days). The study suggests that PAA-UNCPs can potentially be used for long-term targeted imaging and therapy studies in vivo.