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A pilot study in non-human primates shows no adverse response to intravenous injection of quantum dots

Abstract

Quantum dots have been used in biomedical research for imaging1,2, diagnostics3,4 and sensing purposes5,6. However, concerns over the cytotoxicity of their heavy metal constituents7,8 and conflicting results from in vitro7,9 and small animal10,11,12,13,14 toxicity studies have limited their translation towards clinical applications. Here, we show in a pilot study that rhesus macaques injected with phospholipid micelle-encapsulated CdSe/CdS/ZnS quantum dots do not exhibit evidence of toxicity. Blood and biochemical markers remained within normal ranges following treatment, and histology of major organs after 90 days showed no abnormalities. Our results show that acute toxicity of these quantum dots in vivo can be minimal. However, chemical analysis revealed that most of the initial dose of cadmium remained in the liver, spleen and kidneys after 90 days. This means that the breakdown and clearance of quantum dots is quite slow, suggesting that longer-term studies will be required to determine the ultimate fate of these heavy metals and the impact of their persistence in primates.

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Figure 1: Characterization of phospholipid micelle-encapsulated CdSe/CdS/ZnS quantum dot formulation.
Figure 2: Blood test results for treated rhesus macaques.
Figure 3: ICP-MS analysis of the major organs of treated (n = 3) and control (n = 1) rhesus macaques.
Figure 4: Histological images from the major organs of the rhesus macaques three months after intravenous injection of the QD formulation.

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Acknowledgements

This work was supported by The John R. Oishei Foundation, Air Force Office of Scientific Research (grant no. FA95500610398), the Singapore Ministry of Education (Grants Tier 2 MOE2010-T2-2-010 (M4020020.040 ARC2/11) and Tier 1 M4010360.040 RG29/10), Nanyang Technological University (start-up grant no. M4080141.040), the Beijing Natural Science Foundation (no. 7092097) and the National Natural Science Foundation of China (no. 21071150). The authors thank A. Maitra of Johns Hopkins University for helpful discussions.

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K.T.Y. and L.Y. designed the research. K.T.Y, L.Y., R.H., L.L., J.Z., I.R. W.C.L., J.L., K.W., J.L., Y.L. and Y.H. performed the research. L.Y., K.T.Y., L.L., I.R., R.H., J.Z., H.C., W.C.L., J.L., K.W., J.L., Y.L., Y.H., X.Z., M.T.S. and P.N.P. analysed the data. K.T.Y., L.Y., I.R., M.T.S. and P.N.P. co-wrote the paper.

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Correspondence to Ling Ye, Ken-Tye Yong or Paras N. Prasad.

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Ye, L., Yong, KT., Liu, L. et al. A pilot study in non-human primates shows no adverse response to intravenous injection of quantum dots. Nature Nanotech 7, 453–458 (2012). https://doi.org/10.1038/nnano.2012.74

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