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Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo

Abstract

A solid tumor is an organ composed of cancer and host cells embedded in an extracellular matrix and nourished by blood vessels. A prerequisite to understanding tumor pathophysiology is the ability to distinguish and monitor each component in dynamic studies. Standard fluorophores hamper simultaneous intravital imaging of these components. Here, we used multiphoton microscopy techniques and transgenic mice that expressed green fluorescent protein, and combined them with the use of quantum dot preparations. We show that these fluorescent semiconductor nanocrystals can be customized to concurrently image and differentiate tumor vessels from both the perivascular cells and the matrix. Moreover, we used them to measure the ability of particles of different sizes to access the tumor. Finally, we successfully monitored the recruitment of quantum dot–labeled bone marrow–derived precursor cells to the tumor vasculature. These examples show the versatility of quantum dots for studying tumor pathophysiology and creating avenues for treatment.

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Figure 1: Spectra corresponding to representative quantum dots used in this study.
Figure 2: Vascular imaging with quantum dots.
Figure 3: Quantum dot–loaded beads as drug delivery vehicle.
Figure 4: Cell labeling and tracking using quantum dot–TAT bioconjugate.

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Acknowledgements

We thank J. Kahn and S. Roberge for their assistance with the animal preparations. We wish to acknowledge Y.T. Chan, P. Snee, J.S. Steckel and J.B. Tracy for their help with quantum dot synthesis, and R.J. Klein for the separation of bone marrow lineage-negative cells. This work was supported by a National Cancer Institute fellowship to M.S. (F32 CA103386), a US National Institutes of Health grant (5RO1 EB001961-06) to V.T., and a Bioengineering Research Partnership Grant (R24CA85140) and Program Project Grant (P01CA80124) to R.K.J. and D.F. This work was also supported by grants to M.G.B. from the National Science Foundation (NSF-CHE-020989) and the Army Research Office through the Institute for Collaborative Biotechnologies. D.G.D. is a Cancer Research Institute fellow.

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Correspondence to Rakesh K Jain.

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Supplementary information

Supplementary Fig. 1

Quantum dot micelle preparation did not accumulate in extravascular space. (PDF 240 kb)

Supplementary Movie 1

Vessel enhancement using fluorescence-labeled dextran 2,000,000 MW infusion. (AVI 968 kb)

Supplementary Movie 2

Vessel enhancement using quantum dot infusion. (AVI 1806 kb)

Supplementary Movie 3

Ex vivo quantum dot labeling of cells. (AVI 5579 kb)

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Stroh, M., Zimmer, J., Duda, D. et al. Quantum dots spectrally distinguish multiple species within the tumor milieu in vivo. Nat Med 11, 678–682 (2005). https://doi.org/10.1038/nm1247

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