In Vivo Pharmacokinetics, Long-Term Biodistribution and Toxicology Study of Functionalized Upconversion Nanoparticles in Mice

Abstract

Aims: We investigated the in vivo pharmacokinetics, long-term biodistribution and toxicology of polymer-coated upconversion nanoparticles (UCNPs) in mice. Materials & Methods: Near infrared emitting Yb³⁺/Tm³⁺-doped NaYF₄ UCNPs coated with either polyethylene glycol (PEG) or polyacrylic acid (PAA) were intravenously injected into mice. Blood levels of UCNPs were measured. Yttrium levels in various organs were measured to determine the biodistribution of UCNPs over 3 months. Serum biochemistry, hematology and histology assays were conducted for in vivo toxicology assays. Results: UCNP-PEG exhibited improved stability in physiological solutions and prolonged blood circulation half-lives more than UCNP-PAA. No noticeable toxic side effect was noticed for either UCNP-PAA or UCNP-PEG in our toxicology study, despite the long-term retention of those nanoparticles in the reticuloendothelial systems including the liver and spleen of mice. Conclusion: Although more systematic investigations are still required, the absence of appreciable toxicity shown in our study encourages future explorations of UCNPs for in vivo biomedical applications.

Revised submitted: 29/10/2010; Revised submitted: 19/02/2011

Keywords::

• biodistribution
• pharmacokinetics
• toxicology
• upconversion nanoparticle

Financial & competing interests disclosure

This work was partially supported by the National Natural Science Foundation of China (51002100) and a National ‘973’ Program of China (2011CB911002). Liang Cheng was supported by the Innovation Program of Graduate Students in Jiangsu Province (CX10B_036Z). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was partially supported by the National Natural Science Foundation of China (51002100) and a National ‘973’ Program of China (2011CB911002). Liang Cheng was supported by the Innovation Program of Graduate Students in Jiangsu Province (CX10B_036Z). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.