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

Journal name:
Nature Nanotechnology
Year published:
Published online


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.

At a glance


  1. Characterization of phospholipid micelle-encapsulated CdSe/CdS/ZnS quantum dot formulation.
    Figure 1: Characterization of phospholipid micelle-encapsulated CdSe/CdS/ZnS quantum dot formulation.

    a, UV–vis absorbance and photoluminescence emission spectra of micelle-encapsulated quantum dots. The excitonic peaks near the absorption edge and the narrow emission peak show that the quantum dots are relatively monodisperse and defect free. b, Dynamic light scattering data showing the distribution of hydrodynamic diameter of the micelles encapsulating the quantum dots. The blue line is a Gaussan fit with a mean of 52 nm and standard deviation of 12.7 nm. c,d, Transmission electron microscopy (TEM) images showing quantum dots before (c) and after (d) micelle encapsulation. The average diameter of the quantum dots is 7–8 nm. TEM grids were prepared by drop-casting from chloroform (c) or water (d) dispersions and allowing the solvent to evaporate. After encapsulation, the particles remain clustered in groups that are representative of single micelles with multiple encapsulated quantum dots.

  2. Blood test results for treated rhesus macaques.
    Figure 2: Blood test results for treated rhesus macaques.

    ax, The results (n = 6, measured weekly) show no abnormalities in immune response, kidney or liver function, blood clotting or blood chemistry over the 90 day period following treatment. The region rendered in pink represents the normal range from the literature, and the blue region represents the range observed in the test subjects before treatment. Error bars represent one standard deviation above or below the mean. Abbreviations: haemoglobin, Hb; red blood cell count, RBC; white blood cell count, WBC; neutrophil granulocyte, NE; lymphocyte, LY; monocyte, MO; eosinophil granulocyte, EOS; basophil granulocyte, BA; platelet count, PLT; haematocrit, Hct; alkaline phosphatase, ALP; total protein, TPROT; albumin, ALB; total bilirubin, TBILI; direct bilirubin, DBIL; alanine transaminase, ALT; aspartate transaminase, AST; gamma glutamyl transferase, γ-GT; prothrombin time, PT; blood urea nitrogen, BUN; creatinine, CRE; blood glucose, GLU; triglyceride, TG; total cholesterol, CHO.

  3. ICP-MS analysis of the major organs of treated (n = 3) and control (n = 1) rhesus macaques.
    Figure 3: ICP-MS analysis of the major organs of treated (n = 3) and control (n = 1) rhesus macaques.

    Most of the injected dose remained in the kidneys, liver and spleen 90 days after injection. ICP-MS analysis of blood samples at select time points showed rapid clearance of quantum dots from the bloodstream. ac, In vivo biodistribution of cadmium (a), selenium (b) and zinc (c). d, Blood clearance profile of quantum dots. Error bars indicate plus and minus one standard deviation of the measurements from the tissues of three treated animals..

  4. Histological images from the major organs of the rhesus macaques three months after intravenous injection of the QD formulation.
    Figure 4: Histological images from the major organs of the rhesus macaques three months after intravenous injection of the QD formulation.

    Evaluations were carried out by pathologists and found no anomalies. In each pair, the left image is from the control animal and the right image is from a treated animal. ai, Tissues were collected from brain (a), heart (b), liver (c), spleen (d), lung (e), kidney (f), lymph (g), intestine (h) and skin (i). Images were taken at ×40 magnification with standard haematoxylin and eosin staining. Histological images from three additional treated monkeys are provided in Supplementary Figs S2–S4.


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Author information

  1. These authors contributed equally to this work

    • Ling Ye &
    • Ken-Tye Yong


  1. Institute of Gerontology and Geriatrics, Laboratory Animal Center, Chinese PLA General Hospital, Beijing 100853, PR China

    • Ling Ye,
    • Jianwei Liu,
    • Kai Wang,
    • Jing Liu,
    • Yaqian Liu &
    • Yazhuo Hu
  2. School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798, Singapore

    • Ken-Tye Yong &
    • Rui Hu
  3. Institute for Lasers, Photonics and Biophotonics, University at Buffalo, The State University of New York, Buffalo, New York 14260-4200, USA

    • Ken-Tye Yong,
    • Indrajit Roy,
    • Rui Hu,
    • Jing Zhu,
    • Wing-Cheung Law,
    • Mark T. Swihart &
    • Paras N. Prasad
  4. ChangChun University of Science and Technology (CUST), ChangChun, Jilin, 130022, PR China

    • Liwei Liu,
    • Hongxing Cai &
    • Xihe Zhang


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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